P0DP24 · CALM2_HUMAN
- ProteinCalmodulin-2
- GeneCALM2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids149 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:26969752, PubMed:27165696).
Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:26969752, PubMed:27165696, PubMed:35568036).
Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:26969752, PubMed:27165696, PubMed:35568036).
Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425).
Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752).
Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).
Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:26969752, PubMed:27165696, PubMed:35568036).
Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:26969752, PubMed:27165696, PubMed:35568036).
Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425).
Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752).
Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).
(Microbial infection) Required for C.violaceum CopC and S.flexneri OspC3 arginine ADP-riboxanase activity.
Miscellaneous
This protein has four functional calcium-binding sites.
Activity regulation
(Microbial infection) Inactivated by S.flexneri OspC1 and OspC3 proteins, which specifically bind the apo-form of calmodulin, thereby preventing calcium-binding and activity.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 21 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 23 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 25 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 27 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 32 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 57 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 59 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 61 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 63 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 68 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 94 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 96 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 98 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 100 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 105 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 130 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 132 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 134 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 136 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 141 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCalmodulin-2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP0DP24
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Distributed throughout the cell during interphase, but during mitosis becomes dramatically localized to the spindle poles and the spindle microtubules.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Long QT syndrome 15 (LQT15)
- Note
- DescriptionA form of long QT syndrome, a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
- See alsoMIM:616249
Natural variants in LQT15
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_073276 | 96 | D>V | in LQT15; reduction in calcium affinity; highly decreased calcium-dependent inactivation of L-type calcium channel; increased action potential duration; not changed protein abundance; not changed structure; increased thermal stability in absence of calcium; decreased thermal stability in presence of calcium; significantly increased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; dbSNP:rs730882254 | |
VAR_073277 | 98 | N>I | in LQT15; reduction in calcium affinity; dbSNP:rs398124647 | |
VAR_078543 | 98 | N>S | in LQT15; the mutant has significantly reduced calcium affinity compared to wild-type; calmodulin-RYR2 interaction is defective at low intracellular Ca2+ concentrations and restored at moderate to high Ca2+ concentrations; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; significantly reduced ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; dbSNP:rs398124647 | |
VAR_078544 | 130 | D>G | in LQT15; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; significantly decreased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; dbSNP:rs1573214163 | |
VAR_078262 | 130 | D>V | in LQT15 | |
VAR_073279 | 132 | D>E | in LQT15; reduction in calcium affinity; dbSNP:rs398124648 | |
VAR_073280 | 134 | D>H | in LQT15; reduction in calcium affinity; dbSNP:rs398124650 | |
VAR_073281 | 136 | Q>P | in LQT15; reduction in calcium affinity; dbSNP:rs398124649 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_073276 | 96 | in LQT15; reduction in calcium affinity; highly decreased calcium-dependent inactivation of L-type calcium channel; increased action potential duration; not changed protein abundance; not changed structure; increased thermal stability in absence of calcium; decreased thermal stability in presence of calcium; significantly increased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; dbSNP:rs730882254 | |||
Sequence: D → V | ||||||
Natural variant | VAR_073277 | 98 | in LQT15; reduction in calcium affinity; dbSNP:rs398124647 | |||
Sequence: N → I | ||||||
Natural variant | VAR_078543 | 98 | in LQT15; the mutant has significantly reduced calcium affinity compared to wild-type; calmodulin-RYR2 interaction is defective at low intracellular Ca2+ concentrations and restored at moderate to high Ca2+ concentrations; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; significantly reduced ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; dbSNP:rs398124647 | |||
Sequence: N → S | ||||||
Natural variant | VAR_078544 | 130 | in LQT15; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; significantly decreased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; dbSNP:rs1573214163 | |||
Sequence: D → G | ||||||
Natural variant | VAR_078262 | 130 | in LQT15 | |||
Sequence: D → V | ||||||
Natural variant | VAR_073279 | 132 | in LQT15; reduction in calcium affinity; dbSNP:rs398124648 | |||
Sequence: D → E | ||||||
Natural variant | VAR_073280 | 134 | in LQT15; reduction in calcium affinity; dbSNP:rs398124650 | |||
Sequence: D → H | ||||||
Natural variant | VAR_073281 | 136 | in LQT15; reduction in calcium affinity; dbSNP:rs398124649 | |||
Sequence: Q → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 94 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000439933 | 2-149 | UniProt | Calmodulin-2 | |||
Sequence: ADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK | |||||||
Modified residue | 22 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Cross-link | 22 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Cross-link | 22 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate | ||||
Sequence: K | |||||||
Modified residue | 45 | UniProt | Phosphothreonine; by CaMK4 | ||||
Sequence: T | |||||||
Modified residue | 82 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 82 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 95 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 100 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 100 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 102 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 102 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 111 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 116 | UniProt | N6,N6,N6-trimethyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 116 | UniProt | N6-methyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 139 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 139 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Ubiquitination results in a strongly decreased activity.
Phosphorylation results in a decreased activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with MYO1C, MYO5A and RRAD. Interacts with MYO10 (By similarity).
Interacts with CEP97, CCP110, TTN/titin and SRY (PubMed:12871148, PubMed:15746192, PubMed:16760425, PubMed:17719545, PubMed:9804419).
Interacts with USP6; the interaction is calcium dependent (PubMed:16127172).
Interacts with CDK5RAP2 (PubMed:20466722).
Interacts with SCN5A (By similarity).
Interacts with RYR1 (PubMed:18650434).
Interacts with FCHO1 (PubMed:22484487).
Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure (By similarity).
Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity).
Interacts with IQCF1 (By similarity).
Interacts with SYT7 (By similarity).
Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity).
Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434, PubMed:26164367, PubMed:27516456).
Interacts with PCP4; regulates calmodulin calcium-binding (PubMed:27876793).
Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (PubMed:27564677).
Component of the SIFI complex (PubMed:25582440, PubMed:38297121).
Interacts with CEP97, CCP110, TTN/titin and SRY (PubMed:12871148, PubMed:15746192, PubMed:16760425, PubMed:17719545, PubMed:9804419).
Interacts with USP6; the interaction is calcium dependent (PubMed:16127172).
Interacts with CDK5RAP2 (PubMed:20466722).
Interacts with SCN5A (By similarity).
Interacts with RYR1 (PubMed:18650434).
Interacts with FCHO1 (PubMed:22484487).
Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure (By similarity).
Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity).
Interacts with IQCF1 (By similarity).
Interacts with SYT7 (By similarity).
Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity).
Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434, PubMed:26164367, PubMed:27516456).
Interacts with PCP4; regulates calmodulin calcium-binding (PubMed:27876793).
Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (PubMed:27564677).
Component of the SIFI complex (PubMed:25582440, PubMed:38297121).
(Microbial infection) Interacts with C.violaceum CopC (PubMed:35338844, PubMed:35446120, PubMed:36423631).
C.violaceum CopC interacts specifically with the apo form of calmodulin (PubMed:35446120, PubMed:36423631).
C.violaceum CopC interacts specifically with the apo form of calmodulin (PubMed:35446120, PubMed:36423631).
(Microbial infection) Interacts with S.flexneri OspC1 and OspC3 (PubMed:35568036, PubMed:36624349).
S.flexneri OspC1 and OspC3 interact specifically with the apo form of calmodulin and prevents calcium-binding (PubMed:35568036).
S.flexneri OspC1 and OspC3 interact specifically with the apo form of calmodulin and prevents calcium-binding (PubMed:35568036).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-43 | EF-hand 1 | ||||
Sequence: EQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQN | ||||||
Domain | 44-79 | EF-hand 2 | ||||
Sequence: PTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKD | ||||||
Region | 77-149 | Necessary and sufficient for interaction with PCP4 | ||||
Sequence: MKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK | ||||||
Domain | 81-116 | EF-hand 3 | ||||
Sequence: DSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK | ||||||
Domain | 117-149 | EF-hand 4 | ||||
Sequence: LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK |
Sequence similarities
Belongs to the calmodulin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length149
- Mass (Da)16,838
- Last updated2017-05-10 v1
- Checksum6B4BC3FCDE10727B
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 124 | in Ref. 7; AAH08437 | ||||
Sequence: E → Q |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M19311 EMBL· GenBank· DDBJ | AAA35641.1 EMBL· GenBank· DDBJ | mRNA | ||
D45887 EMBL· GenBank· DDBJ | BAA08302.1 EMBL· GenBank· DDBJ | mRNA | ||
U94728 EMBL· GenBank· DDBJ | AAC83174.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U94725 EMBL· GenBank· DDBJ | AAC83174.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U94726 EMBL· GenBank· DDBJ | AAC83174.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT009916 EMBL· GenBank· DDBJ | AAP88918.1 EMBL· GenBank· DDBJ | mRNA | ||
CR541990 EMBL· GenBank· DDBJ | CAG46787.1 EMBL· GenBank· DDBJ | mRNA | ||
CR542021 EMBL· GenBank· DDBJ | CAG46818.1 EMBL· GenBank· DDBJ | mRNA | ||
AC073283 EMBL· GenBank· DDBJ | AAY24085.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC003354 EMBL· GenBank· DDBJ | AAH03354.1 EMBL· GenBank· DDBJ | mRNA | ||
BC006464 EMBL· GenBank· DDBJ | AAH06464.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008437 EMBL· GenBank· DDBJ | AAH08437.1 EMBL· GenBank· DDBJ | mRNA | ||
BC017385 EMBL· GenBank· DDBJ | AAH17385.1 EMBL· GenBank· DDBJ | mRNA | ||
BC018677 EMBL· GenBank· DDBJ | AAH18677.1 EMBL· GenBank· DDBJ | mRNA | ||
BC026065 EMBL· GenBank· DDBJ | AAH26065.1 EMBL· GenBank· DDBJ | mRNA |