UniProtKB - P0DP25 (CALM3_HUMAN)
Calmodulin-3
CALM3
Functioni
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269).
Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.
By similarity2 PublicationsMiscellaneous
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Calcium bindingi | 21 – 32 | 11 PublicationAdd BLAST | 12 | |
Calcium bindingi | 57 – 68 | 21 PublicationAdd BLAST | 12 | |
Calcium bindingi | 94 – 105 | 31 PublicationAdd BLAST | 12 | |
Calcium bindingi | 130 – 141 | 41 PublicationAdd BLAST | 12 |
GO - Molecular functioni
- adenylate cyclase activator activity Source: UniProtKB
- adenylate cyclase binding Source: CAFA
- calcium-dependent protein binding Source: Ensembl
- calcium ion binding Source: UniProtKB
- disordered domain specific binding Source: CAFA
- enzyme regulator activity Source: GO_Central
- nitric-oxide synthase binding Source: Ensembl
- nitric-oxide synthase regulator activity Source: Ensembl
- N-terminal myristoylation domain binding Source: UniProtKB
- phosphatidylinositol 3-kinase binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein kinase binding Source: BHF-UCL
- protein phosphatase activator activity Source: BHF-UCL
- protein serine/threonine kinase activator activity Source: BHF-UCL
- titin binding Source: BHF-UCL
- transmembrane transporter binding Source: BHF-UCL
- type 3 metabotropic glutamate receptor binding Source: Ensembl
GO - Biological processi
- activation of adenylate cyclase activity Source: Ensembl
- detection of calcium ion Source: BHF-UCL
- establishment of protein localization to mitochondrial membrane Source: Ensembl
- G2/M transition of mitotic cell cycle Source: Ensembl
- G protein-coupled receptor signaling pathway Source: UniProtKB
- negative regulation of calcium ion export across plasma membrane Source: Ensembl
- negative regulation of high voltage-gated calcium channel activity Source: UniProtKB
- negative regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
- negative regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
- positive regulation of apoptotic process Source: ComplexPortal
- positive regulation of autophagic cell death Source: ComplexPortal
- positive regulation of cyclic-nucleotide phosphodiesterase activity Source: BHF-UCL
- positive regulation of DNA binding Source: Ensembl
- positive regulation of nitric-oxide synthase activity Source: Ensembl
- positive regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
- positive regulation of phosphoprotein phosphatase activity Source: BHF-UCL
- positive regulation of protein autophosphorylation Source: BHF-UCL
- positive regulation of protein dephosphorylation Source: BHF-UCL
- positive regulation of protein serine/threonine kinase activity Source: BHF-UCL
- positive regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
- potassium ion transmembrane transport Source: ComplexPortal
- protein autophosphorylation Source: ComplexPortal
- regulation of calcium-mediated signaling Source: Ensembl
- regulation of cardiac muscle cell action potential Source: UniProtKB
- regulation of cardiac muscle contraction Source: BHF-UCL
- regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
- regulation of cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
- regulation of cytokinesis Source: UniProtKB
- regulation of heart rate Source: BHF-UCL
- regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
- regulation of response to tumor cell Source: ComplexPortal
- regulation of synaptic vesicle endocytosis Source: Ensembl
- regulation of synaptic vesicle exocytosis Source: Ensembl
- response to amphetamine Source: Ensembl
- response to calcium ion Source: BHF-UCL
- response to corticosterone Source: Ensembl
- substantia nigra development Source: UniProtKB
Keywordsi
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | P0DP25 |
SignaLinki | P0DP25 |
SIGNORi | P0DP25 |
Names & Taxonomyi
Protein namesi | Recommended name: Calmodulin-3Imported |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1449, CALM3 |
MIMi | 114183, gene |
neXtProti | NX_P0DP25 |
VEuPathDBi | HostDB:ENSG00000160014 |
Subcellular locationi
Cytoskeleton
- spindle 1 Publication
- spindle pole 1 Publication
- centrosome 1 Publication
Note: Distributed throughout the cell during interphase, but during mitosis becomes dramatically localized to the spindle poles and the spindle microtubules.
Cytoskeleton
- centrosome Source: UniProtKB
- spindle microtubule Source: UniProtKB
- spindle pole Source: UniProtKB
Mitochondrion
- mitochondrial membrane Source: Ensembl
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
- voltage-gated potassium channel complex Source: ComplexPortal
Other locations
- calcium channel complex Source: BHF-UCL
- catalytic complex Source: CAFA
- cytoplasm Source: UniProtKB
- DAPK1-calmodulin complex Source: ComplexPortal
- growth cone Source: Ensembl
- myelin sheath Source: Ensembl
- protein-containing complex Source: CAFA
- sarcomere Source: BHF-UCL
- synaptic vesicle membrane Source: Ensembl
- vesicle Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, CytoskeletonPathology & Biotechi
Involvement in diseasei
Ventricular tachycardia, catecholaminergic polymorphic, 6 (CPVT6)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078261 | 103 | A → V in CPVT6; decreased calcium-binding affinity; not changed binding to RYR2; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed action potential duration. 1 Publication | 1 |
Long QT syndrome 16 (LQT16)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083815 | 130 | D → G in LQT16. 2 Publications | 1 | |
Natural variantiVAR_083816 | 141 | E → K in LQT16; loss-of-function variant causing impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential; decreased calcium ion binding. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Long QT syndromeOrganism-specific databases
DisGeNETi | 801 805 808 |
MalaCardsi | CALM3 |
MIMi | 618782, phenotype |
OpenTargetsi | ENSG00000143933 ENSG00000160014 ENSG00000198668 |
Orphaneti | 3286, Catecholaminergic polymorphic ventricular tachycardia 101016, Romano-Ward syndrome |
Miscellaneous databases
Pharosi | P0DP25, Tclin |
Chemistry databases
DrugBanki | DB11093, Calcium citrate DB11348, Calcium Phosphate DB14481, Calcium phosphate dihydrate |
DrugCentrali | P0DP25 |
Genetic variation databases
BioMutai | CALM3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources2 Publications | |||
ChainiPRO_0000439934 | 2 – 149 | Calmodulin-3Add BLAST | 148 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources2 Publications | 1 | |
Modified residuei | 22 | N6-acetyllysine; alternateCombined sources | 1 | |
Cross-linki | 22 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources | ||
Cross-linki | 22 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity | ||
Modified residuei | 45 | Phosphothreonine; by CaMK4By similarity | 1 | |
Modified residuei | 82 | PhosphoserineCombined sources | 1 | |
Modified residuei | 95 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 100 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 102 | PhosphoserineCombined sources | 1 | |
Modified residuei | 111 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 116 | N6,N6,N6-trimethyllysine; alternateCombined sources1 Publication | 1 | |
Modified residuei | 116 | N6-methyllysine; alternateCombined sources | 1 | |
Modified residuei | 139 | PhosphotyrosineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P0DP25 |
jPOSTi | P0DP25 |
MassIVEi | P0DP25 |
PTM databases
GlyGeni | P0DP25, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P0DP25 |
MetOSitei | P0DP25 |
Expressioni
Gene expression databases
ExpressionAtlasi | P0DP25, baseline and differential |
Organism-specific databases
HPAi | ENSG00000160014, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Interacts with MYO1C, MYO5A and RRAD.
Interacts with MYO10 (By similarity).
Interacts with CEP97, CCP110, TTN/titin and SRY (PubMed:9804419, PubMed:12871148, PubMed:15746192, PubMed:16760425, PubMed:17719545).
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:27516456, PubMed:18650434).
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).
By similarity13 PublicationsGO - Molecular functioni
- adenylate cyclase binding Source: CAFA
- calcium-dependent protein binding Source: Ensembl
- disordered domain specific binding Source: CAFA
- nitric-oxide synthase binding Source: Ensembl
- N-terminal myristoylation domain binding Source: UniProtKB
- phosphatidylinositol 3-kinase binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein kinase binding Source: BHF-UCL
- titin binding Source: BHF-UCL
- transmembrane transporter binding Source: BHF-UCL
- type 3 metabotropic glutamate receptor binding Source: Ensembl
Protein-protein interaction databases
MINTi | P0DP25 |
Chemistry databases
BindingDBi | P0DP25 |
Miscellaneous databases
RNActi | P0DP25, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P0DP25 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 8 – 43 | EF-hand 1PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 44 – 79 | EF-hand 2PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 81 – 116 | EF-hand 3PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 117 – 149 | EF-hand 4PROSITE-ProRule annotationAdd BLAST | 33 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 77 – 149 | Necessary and sufficient for interaction with PCP41 PublicationAdd BLAST | 73 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
GeneTreei | ENSGT00950000182980 |
OMAi | HQIEFDE |
OrthoDBi | 1386217at2759 |
Family and domain databases
CDDi | cd00051, EFh, 2 hits |
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom |
Pfami | View protein in Pfam PF13499, EF-hand_7, 2 hits |
SMARTi | View protein in SMART SM00054, EFh, 4 hits |
SUPFAMi | SSF47473, SSF47473, 1 hit |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 4 hits PS50222, EF_HAND_2, 4 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ
60 70 80 90 100
DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREAF RVFDKDGNGY
110 120 130 140
ISAAELRHVM TNLGEKLTDE EVDEMIREAD IDGDGQVNYE EFVQMMTAK
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078261 | 103 | A → V in CPVT6; decreased calcium-binding affinity; not changed binding to RYR2; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed action potential duration. 1 Publication | 1 | |
Natural variantiVAR_083815 | 130 | D → G in LQT16. 2 Publications | 1 | |
Natural variantiVAR_083816 | 141 | E → K in LQT16; loss-of-function variant causing impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential; decreased calcium ion binding. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04046 mRNA Translation: AAA51918.1 X52606, X52607, X52608 Genomic DNA Translation: CAA36839.1 Sequence problems. BT006855 mRNA Translation: AAP35501.1 AC093503 Genomic DNA No translation available. BC005137 mRNA Translation: AAH05137.1 |
CCDSi | CCDS33061.1 CCDS86782.1 |
RefSeqi | NP_001316851.1, NM_001329922.1 NP_001316852.1, NM_001329923.1 NP_001316853.1, NM_001329924.1 NP_001316854.1, NM_001329925.1 NP_001316855.1, NM_001329926.1 NP_001734.1, NM_001743.5 NP_005175.2, NM_005184.3 NP_008819.1, NM_006888.4 |
Genome annotation databases
Ensembli | ENST00000291295; ENSP00000291295; ENSG00000160014 ENST00000596362; ENSP00000472141; ENSG00000160014 |
GeneIDi | 801 805 808 |
KEGGi | hsa:801 hsa:805 hsa:808 |
MANE-Selecti | ENST00000272298.12; ENSP00000272298.7; NM_001743.6; NP_001734.1 ENST00000291295.14; ENSP00000291295.8; NM_005184.4; NP_005175.2 ENST00000356978.9; ENSP00000349467.4; NM_006888.6; NP_008819.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04046 mRNA Translation: AAA51918.1 X52606, X52607, X52608 Genomic DNA Translation: CAA36839.1 Sequence problems. BT006855 mRNA Translation: AAP35501.1 AC093503 Genomic DNA No translation available. BC005137 mRNA Translation: AAH05137.1 |
CCDSi | CCDS33061.1 CCDS86782.1 |
RefSeqi | NP_001316851.1, NM_001329922.1 NP_001316852.1, NM_001329923.1 NP_001316853.1, NM_001329924.1 NP_001316854.1, NM_001329925.1 NP_001316855.1, NM_001329926.1 NP_001734.1, NM_001743.5 NP_005175.2, NM_005184.3 NP_008819.1, NM_006888.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5COC | X-ray | 2.67 | A | 7-78 | [»] | |
5J03 | X-ray | 2.00 | B | 1-149 | [»] | |
6K67 | X-ray | 1.95 | B/D | 9-81 | [»] | |
7BYL | electron microscopy | 2.50 | B/D/F/H | 1-149 | [»] | |
7BYM | electron microscopy | 3.10 | B/D/F/H | 1-149 | [»] | |
7BYN | electron microscopy | 3.30 | B/D/F/H | 1-149 | [»] | |
7CR3 | electron microscopy | 3.60 | C/E/F/H | 1-149 | [»] | |
7CR4 | electron microscopy | 3.90 | C/E/G/H | 1-149 | [»] | |
7CR7 | electron microscopy | 3.70 | C/E/F/H | 1-149 | [»] | |
SMRi | P0DP25 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
MINTi | P0DP25 |
Chemistry databases
BindingDBi | P0DP25 |
DrugBanki | DB11093, Calcium citrate DB11348, Calcium Phosphate DB14481, Calcium phosphate dihydrate |
DrugCentrali | P0DP25 |
PTM databases
GlyGeni | P0DP25, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P0DP25 |
MetOSitei | P0DP25 |
Genetic variation databases
BioMutai | CALM3 |
Proteomic databases
EPDi | P0DP25 |
jPOSTi | P0DP25 |
MassIVEi | P0DP25 |
Protocols and materials databases
Antibodypediai | 39411, 181 antibodies from 17 providers |
DNASUi | 801 |
Genome annotation databases
Organism-specific databases
CTDi | 801 805 808 |
DisGeNETi | 801 805 808 |
GeneCardsi | CALM3 |
HGNCi | HGNC:1449, CALM3 |
HPAi | ENSG00000160014, Tissue enhanced (brain) |
MalaCardsi | CALM3 |
MIMi | 114183, gene 618782, phenotype |
neXtProti | NX_P0DP25 |
OpenTargetsi | ENSG00000143933 ENSG00000160014 ENSG00000198668 |
Orphaneti | 3286, Catecholaminergic polymorphic ventricular tachycardia 101016, Romano-Ward syndrome |
VEuPathDBi | HostDB:ENSG00000160014 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00950000182980 |
OMAi | HQIEFDE |
OrthoDBi | 1386217at2759 |
Enzyme and pathway databases
PathwayCommonsi | P0DP25 |
SignaLinki | P0DP25 |
SIGNORi | P0DP25 |
Miscellaneous databases
BioGRID-ORCSi | 801, 4 hits in 1044 CRISPR screens 805, 32 hits in 926 CRISPR screens 808, 39 hits in 1039 CRISPR screens |
ChiTaRSi | CALM3, human |
Pharosi | P0DP25, Tclin |
PROi | PR:P0DP25 |
RNActi | P0DP25, protein |
SOURCEi | Search... |
Gene expression databases
ExpressionAtlasi | P0DP25, baseline and differential |
Family and domain databases
CDDi | cd00051, EFh, 2 hits |
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom |
Pfami | View protein in Pfam PF13499, EF-hand_7, 2 hits |
SMARTi | View protein in SMART SM00054, EFh, 4 hits |
SUPFAMi | SSF47473, SSF47473, 1 hit |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 4 hits PS50222, EF_HAND_2, 4 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | CALM3_HUMAN | |
Accessioni | P0DP25Primary (citable) accession number: P0DP25 Secondary accession number(s): P02593 Q96HK3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 10, 2017 |
Last sequence update: | May 10, 2017 | |
Last modified: | February 23, 2022 | |
This is version 40 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families