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Protein

Calmodulin-3

Gene

CALM3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. 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 similarity1 Publication

Miscellaneous

This protein has four functional calcium-binding sites.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi21 – 3211 PublicationAdd BLAST12
Calcium bindingi57 – 6821 PublicationAdd BLAST12
Calcium bindingi94 – 10531 PublicationAdd BLAST12
Calcium bindingi130 – 14141 PublicationAdd BLAST12

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandCalcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Calmodulin-3Imported
Gene namesi
Name:CALM3Imported
Synonyms:CALML2, CAM3, CAMC, CAMIII
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1449 CALM3
MIMi114183 gene
neXtProtiNX_P0DP25

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare condition caused by mutation in CALM3 that lead to an arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress.1 Publication

Keywords - Diseasei

Disease mutation, Long QT syndrome

Organism-specific databases

MalaCardsiCALM3
OpenTargetsiENSG00000143933
ENSG00000160014
ENSG00000198668
Orphaneti3286 Catecholaminergic polymorphic ventricular tachycardia

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00004399342 – 149Calmodulin-3Add BLAST148

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources2 Publications1
Modified residuei22N6-acetyllysine; alternateCombined sources1
Cross-linki22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei45Phosphothreonine; by CaMK4By similarity1
Modified residuei82PhosphoserineCombined sources1
Modified residuei95N6-acetyllysineCombined sources1
Modified residuei100PhosphotyrosineCombined sources1
Modified residuei102PhosphoserineCombined sources1
Modified residuei111PhosphothreonineCombined sources1
Modified residuei116N6,N6,N6-trimethyllysine; alternateCombined sources1 Publication1
Modified residuei116N6-methyllysine; alternateCombined sources1
Modified residuei139PhosphotyrosineCombined sources1

Post-translational modificationi

Ubiquitination results in a strongly decreased activity.By similarity
Phosphorylation results in a decreased activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP0DP25

PTM databases

iPTMnetiP0DP25

Expressioni

Gene expression databases

ExpressionAtlasiP0DP25 baseline and differential

Organism-specific databases

HPAiHPA044999

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 to the proper assembly of a functional heterotetrameric M channel (PubMed:27564677).By similarity13 Publications

GO - Molecular functioni

Chemistry databases

BindingDBiP0DP25

Structurei

3D structure databases

SMRiP0DP25
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 43EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini44 – 79EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini81 – 116EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini117 – 149EF-hand 4PROSITE-ProRule annotationAdd BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni77 – 149Necessary and sufficient for interaction with PCP41 PublicationAdd BLAST73

Sequence similaritiesi

Belongs to the calmodulin family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

GeneTreeiENSGT00760000118901
KOiK02183

Family and domain databases

CDDicd00051 EFh, 2 hits
InterProiView protein in InterPro
IPR039030 Calmodulin
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
PANTHERiPTHR23050:SF311 PTHR23050:SF311, 1 hit
PfamiView protein in Pfam
PF13499 EF-hand_7, 2 hits
SMARTiView protein in SMART
SM00054 EFh, 4 hits
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 4 hits
PS50222 EF_HAND_2, 4 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P0DP25-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:149
Mass (Da):16,838
Last modified:May 10, 2017 - v1
Checksum:i6B4BC3FCDE10727B
GO

Sequence cautioni

The sequence CAA36839 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078261103A → V Probable disease-associated mutation found in a patient with CPVT; 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 Publication1

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
CCDSiCCDS33061.1
CCDS86782.1
RefSeqiNP_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
UniGeneiHs.282410
Hs.468442
Hs.515487

Genome annotation databases

EnsembliENST00000291295; ENSP00000291295; ENSG00000160014
ENST00000596362; ENSP00000472141; ENSG00000160014
GeneIDi801
805
808
KEGGihsa:801
hsa:805
hsa:808

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS33061.1
CCDS86782.1
RefSeqiNP_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
UniGeneiHs.282410
Hs.468442
Hs.515487

3D structure databases

SMRiP0DP25
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiP0DP25

PTM databases

iPTMnetiP0DP25

Proteomic databases

PRIDEiP0DP25

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291295; ENSP00000291295; ENSG00000160014
ENST00000596362; ENSP00000472141; ENSG00000160014
GeneIDi801
805
808
KEGGihsa:801
hsa:805
hsa:808

Organism-specific databases

CTDi801
805
808
GeneCardsiCALM3
HGNCiHGNC:1449 CALM3
HPAiHPA044999
MalaCardsiCALM3
MIMi114183 gene
neXtProtiNX_P0DP25
OpenTargetsiENSG00000143933
ENSG00000160014
ENSG00000198668
Orphaneti3286 Catecholaminergic polymorphic ventricular tachycardia
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00760000118901
KOiK02183

Miscellaneous databases

ChiTaRSiCALM3 human
PROiPR:P0DP25
SOURCEiSearch...

Gene expression databases

ExpressionAtlasiP0DP25 baseline and differential

Family and domain databases

CDDicd00051 EFh, 2 hits
InterProiView protein in InterPro
IPR039030 Calmodulin
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
PANTHERiPTHR23050:SF311 PTHR23050:SF311, 1 hit
PfamiView protein in Pfam
PF13499 EF-hand_7, 2 hits
SMARTiView protein in SMART
SM00054 EFh, 4 hits
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 4 hits
PS50222 EF_HAND_2, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCALM3_HUMAN
AccessioniPrimary (citable) accession number: P0DP25
Secondary accession number(s): P02593
, P62158, P70667, P99014, Q13942, Q53S29, Q61379, Q61380, Q96HK3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2017
Last sequence update: May 10, 2017
Last modified: November 7, 2018
This is version 17 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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