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Protein

Calmodulin-1

Gene

CALM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).4 Publications

Miscellaneous

This protein has four functional calcium-binding sites.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi21 – 321Combined sources2 PublicationsAdd BLAST12
Calcium bindingi57 – 682Combined sources2 PublicationsAdd BLAST12
Calcium bindingi94 – 1053Combined sources2 PublicationsAdd BLAST12
Calcium bindingi130 – 1414Combined sources2 PublicationsAdd BLAST12

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandCalcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Calmodulin-1Imported
Gene namesi
Name:CALM11 PublicationImported
Synonyms:CALM, CAM, CAM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:1442. CALM1.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Ventricular tachycardia, catecholaminergic polymorphic, 4 (CPVT4)4 Publications
The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4.
Disease descriptionAn 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. CPVT4 inheritance is autosomal dominant.
See also OMIM:614916
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06922254N → I in CPVT4; increased RYR2 calcium-release channel activity; not changed calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; not changed thermal stability both in the absence and presence of calcium; no effect on the calcium binding affinity; significantly increased binding of RYR2; 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. 4 PublicationsCorresponds to variant dbSNP:rs267607276Ensembl.1
Natural variantiVAR_07854198N → S in CPVT4; the mutant has significantly reduced calcium affinity compared to wild-type; calmodulin-RYR2 interaction is defective at low intracellular Ca(2+) concentrations and restored at moderate to high Ca(2+) 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. 4 PublicationsCorresponds to variant dbSNP:rs398124647Ensembl.1
Long QT syndrome 14 (LQT14)5 Publications
The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.
Disease 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 also OMIM:616247
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07327590F → L in LQT14; significantly decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane. 2 PublicationsCorresponds to variant dbSNP:rs730882253Ensembl.1
Natural variantiVAR_078542130D → G in LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of clacium; 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. 4 PublicationsCorresponds to variant dbSNP:rs730882252Ensembl.1
Natural variantiVAR_078263141E → G in LQT14; decreased calcium affinity; loss of CACNA1C calcium-dependent-inactivation; no effect on intracellular RYR2-mediated calcium release. 1 Publication1
Natural variantiVAR_073282142F → L in LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; no effect on RYR2 interaction; significantly reduced ryanodine-sensitive calcium-release channel activity. 3 PublicationsCorresponds to variant dbSNP:rs11551462Ensembl.1

Keywords - Diseasei

Disease mutation, Long QT syndrome

Organism-specific databases

GeneReviewsiCALM1.
MalaCardsiCALM1.
MIMi614916. phenotype.
616247. phenotype.
OpenTargetsiENSG00000143933.
ENSG00000160014.
ENSG00000198668.

Polymorphism and mutation databases

BioMutaiCALM1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00004399322 – 149Calmodulin-1Add 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

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 (PubMed:21167176). 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 (PubMed:23893133). 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, PubMed:26164367). 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 similarity20 Publications

Structurei

Secondary structure

1149
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 4Combined sources3
Helixi7 – 20Combined sources14
Beta strandi21 – 23Combined sources3
Beta strandi25 – 28Combined sources4
Helixi30 – 39Combined sources10
Helixi46 – 56Combined sources11
Helixi57 – 59Combined sources3
Beta strandi61 – 65Combined sources5
Helixi66 – 93Combined sources28
Beta strandi94 – 96Combined sources3
Beta strandi97 – 101Combined sources5
Helixi103 – 112Combined sources10
Beta strandi113 – 115Combined sources3
Helixi119 – 129Combined sources11
Turni130 – 132Combined sources3
Beta strandi133 – 138Combined sources6
Helixi139 – 146Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AJImodel-A5-148[»]
1CDLX-ray2.00A/B/C/D2-148[»]
1CLLX-ray1.70A2-149[»]
1CTRX-ray2.45A2-149[»]
1IWQX-ray2.00A2-149[»]
1J7ONMR-A2-77[»]
1J7PNMR-A83-149[»]
1K90X-ray2.75D/E/F2-149[»]
1K93X-ray2.95D/E/F6-149[»]
1L7ZX-ray2.30A2-149[»]
1LVCX-ray3.60D/E/F1-149[»]
1NKFNMR-A99-105[»]
1PK0X-ray3.30D/E/F2-148[»]
1S26X-ray3.00D/E/F2-149[»]
1SK6X-ray3.20D/E/F2-149[»]
1SW8NMR-A2-80[»]
1WRZX-ray2.00A1-149[»]
1XFUX-ray3.35O/P/Q/R/S/T1-149[»]
1XFVX-ray3.35O/P/Q/R/S/T1-149[»]
1XFWX-ray3.40O/P/Q/R/S/T1-149[»]
1XFXX-ray3.20O/P/Q/R/S/T1-149[»]
1XFYX-ray3.30O/P/Q/R/S/T1-149[»]
1XFZX-ray3.25O/P/Q/R/S/T1-149[»]
1Y6WX-ray2.40A2-149[»]
1YR5X-ray1.70A2-149[»]
1YRTX-ray2.10B76-149[»]
1YRUX-ray2.50B76-149[»]
1ZOTX-ray2.20B80-148[»]
1ZUZX-ray1.91A1-149[»]
2BE6X-ray2.00A/B/C1-149[»]
2F3YX-ray1.45A2-149[»]
2F3ZX-ray1.60A2-149[»]
2HF5NMR-A47-114[»]
2I08X-ray2.00A3-79[»]
2JZINMR-A2-149[»]
2K0ENMR-A2-149[»]
2K0FNMR-A2-149[»]
2K0JNMR-A3-149[»]
2K61NMR-A2-149[»]
2KNENMR-A2-149[»]
2KUGNMR-A2-77[»]
2KUHNMR-A83-149[»]
2L53NMR-A2-149[»]
2L7LNMR-A2-149[»]
2LGFNMR-A3-149[»]
2LL6NMR-A2-149[»]
2LL7NMR-A2-149[»]
2LQCNMR-A2-78[»]
2LQPNMR-A79-149[»]
2LV6Other-A2-149[»]
2M0JNMR-A2-149[»]
2M0KNMR-A2-149[»]
2M55NMR-A2-149[»]
2MG5NMR-A2-149[»]
2N27NMR-A2-149[»]
2N6ANMR-A6-147[»]
2N77NMR-A77-149[»]
2N8JNMR-A2-149[»]
2R28X-ray1.86A/B1-149[»]
2V01X-ray2.15A2-149[»]
2V02X-ray2.20A2-149[»]
2VAYX-ray1.94A4-149[»]
2W73X-ray1.45A/B/E/F1-149[»]
2WELX-ray1.90D1-149[»]
2X0GX-ray2.20B2-149[»]
2Y4VX-ray1.80A1-149[»]
3BYAX-ray1.85A2-149[»]
3DVEX-ray2.35A2-149[»]
3DVJX-ray2.80A2-149[»]
3DVKX-ray2.30A2-149[»]
3DVMX-ray2.60A2-149[»]
3EWTX-ray2.40A2-149[»]
3EWVX-ray2.60A2-149[»]
3G43X-ray2.10A/B/C/D2-149[»]
3HR4X-ray2.50B/D/F/H1-149[»]
3J41electron microscopy25.0E/F1-149[»]
3O77X-ray2.35A1-149[»]
3O78X-ray2.60A/B1-149[»]
3OXQX-ray2.55A/B/C/D1-149[»]
3SUIX-ray1.95A1-149[»]
3UCTX-ray1.90A/B2-80[»]
3UCWX-ray1.76A/B/C/D2-80[»]
3UCYX-ray1.80A2-80[»]
4BW7X-ray1.81A/C1-149[»]
4BW8X-ray1.80A/B1-149[»]
4BYFX-ray2.74B/D1-149[»]
4DCKX-ray2.20B1-149[»]
4DJCX-ray1.35A1-149[»]
4GOWX-ray2.60D4-147[»]
4JPZX-ray3.02C/I1-149[»]
4JQ0X-ray3.84C1-149[»]
4L79X-ray2.30B1-149[»]
4LZXX-ray1.50A2-149[»]
4M1LX-ray2.10A2-149[»]
4OVNX-ray2.80A/B/C/D/E1-149[»]
4Q57X-ray1.80A10-74[»]
4Q5UX-ray1.95A1-149[»]
4UMOX-ray3.00C/D1-149[»]
4UPUX-ray2.34A2-149[»]
4V0CX-ray2.86C/D1-149[»]
5COCX-ray2.67A5-78[»]
5DBRX-ray2.25A5-149[»]
5DOWX-ray1.70A/C/E/G2-149[»]
5DSUX-ray1.93A3-78[»]
5GGMNMR-A2-149[»]
5I0IX-ray3.15C/E3-147[»]
G84-126[»]
I84-147[»]
5J03X-ray2.00B1-149[»]
5J8HNMR-A2-149[»]
5K7Lelectron microscopy3.78B1-149[»]
5K8QX-ray1.74A1-149[»]
SMRiP0DP23.
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

Family and domain databases

CDDicd00051. EFh. 2 hits.
InterProiView protein in InterPro
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
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.

P0DP23-1 [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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06922254N → I in CPVT4; increased RYR2 calcium-release channel activity; not changed calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; not changed thermal stability both in the absence and presence of calcium; no effect on the calcium binding affinity; significantly increased binding of RYR2; 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. 4 PublicationsCorresponds to variant dbSNP:rs267607276Ensembl.1
Natural variantiVAR_07327590F → L in LQT14; significantly decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane. 2 PublicationsCorresponds to variant dbSNP:rs730882253Ensembl.1
Natural variantiVAR_07854198N → S in CPVT4; the mutant has significantly reduced calcium affinity compared to wild-type; calmodulin-RYR2 interaction is defective at low intracellular Ca(2+) concentrations and restored at moderate to high Ca(2+) 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. 4 PublicationsCorresponds to variant dbSNP:rs398124647Ensembl.1
Natural variantiVAR_078542130D → G in LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of clacium; 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. 4 PublicationsCorresponds to variant dbSNP:rs730882252Ensembl.1
Natural variantiVAR_078263141E → G in LQT14; decreased calcium affinity; loss of CACNA1C calcium-dependent-inactivation; no effect on intracellular RYR2-mediated calcium release. 1 Publication1
Natural variantiVAR_073282142F → L in LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; no effect on RYR2 interaction; significantly reduced ryanodine-sensitive calcium-release channel activity. 3 PublicationsCorresponds to variant dbSNP:rs11551462Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27319 mRNA. Translation: AAA35635.1.
U12022, U11886 Genomic DNA. Translation: AAB60644.1.
BT006818 mRNA. Translation: AAP35464.1.
AC006536 Genomic DNA. Translation: AAD45181.1.
AL512791 Genomic DNA. No translation available.
BC000454 mRNA. Translation: AAH00454.1.
BC008597 mRNA. Translation: AAH08597.1.
BC011834 mRNA. Translation: AAH11834.1.
BC047523 mRNA. No translation available.
CCDSiCCDS9892.1.
PIRiS48728. MCHU.
RefSeqiNP_001316851.1. NM_001329922.1.
NP_001734.1. NM_001743.5.
NP_005175.2. NM_005184.3.
NP_008819.1. NM_006888.4.

Genome annotation databases

EnsembliENST00000356978; ENSP00000349467; ENSG00000198668.
GeneIDi801.
805.
808.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCALM1_HUMAN
AccessioniPrimary (citable) accession number: P0DP23
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: August 30, 2017
This is version 4 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families