UniProt functional annotation for P0DP23



	UniProt functional annotation for P0DP23

UniProt codes: P0DP23, P02593.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endomplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335). {ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:23893133, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:31454269}.

Function: (Microbial infection) Required for Legionella pneumophila SidJ glutamylase activity. {ECO:0000269|PubMed:31330532}.

Subunit: 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 in the proper assembly of a functional heterotetrameric M channel (PubMed:27564677). Interacts with alpha-synuclein/SNCA (PubMed:23607618). Interacts with SLC9A1 in a calcium-dependent manner (PubMed:30287853). In the absence of Ca(+2), interacts with GIMAP4 (via IQ domain) (By similarity). Interacts with SCN8A; the interaction modulates the inactivation rate of SCN8A (By similarity). Interaction with KIF1A; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility (PubMed:30021165). Interacts with KCNN3 (PubMed:31155282). Interacts with KCNQ1 (via C-terminus); forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (PubMed:18165683,PubMed:25441029). Interacts with PIK3C3; the interaction modulates PIK3C3 kinase activity (PubMed:28890335). {ECO:0000250|UniProtKB:P0DP26, ECO:0000250|UniProtKB:P62157, ECO:0000250|UniProtKB:P62161, ECO:0000250|UniProtKB:P62204, ECO:0000269|PubMed:12485993, ECO:0000269|PubMed:12577052, ECO:0000269|PubMed:12871148, ECO:0000269|PubMed:15719022, ECO:0000269|PubMed:15746192, ECO:0000269|PubMed:16127172, ECO:0000269|PubMed:16299511, ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:17719545, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:18650434, ECO:0000269|PubMed:20466722, ECO:0000269|PubMed:21167176, ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:23109337, ECO:0000269|PubMed:23607618, ECO:0000269|PubMed:23893133, ECO:0000269|PubMed:25441029, ECO:0000269|PubMed:26164367, ECO:0000269|PubMed:27516456, ECO:0000269|PubMed:27564677, ECO:0000269|PubMed:27876793, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:30021165, ECO:0000269|PubMed:30287853, ECO:0000269|PubMed:31155282, ECO:0000269|PubMed:9804419}.

Subunit: (Microbial infection) Interacts with Rubella virus protease/methyltransferase p150. {ECO:0000269|PubMed:20086014}.

Subunit: (Microbial infection) Interacts with Legionella pneumophila glutamylase SidJ. {ECO:0000269|PubMed:31330532}.

Subcellular location: Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:16760425}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:16760425}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:14654843}. Note=Distributed throughout the cell during interphase, but during mitosis becomes dramatically localized to the spindle poles and the spindle microtubules.

Domain: The N-terminal and C-terminal lobes of CALM bind to the C- terminus of KCNQ1 in a clamp-like conformation. Binding of CALM C- terminus to KCNQ1 is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to KCNQ1 is calcium- dependent and regulates electrophysiological activity of the channel. {ECO:0000269|PubMed:25441029}.

Ptm: Ubiquitination results in a strongly decreased activity. {ECO:0000250}.

Ptm: Phosphorylation results in a decreased activity. {ECO:0000250}.

Disease: Ventricular tachycardia, catecholaminergic polymorphic, 4 (CPVT4) [MIM:614916]: 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. CPVT4 inheritance is autosomal dominant. {ECO:0000269|PubMed:23040497, ECO:0000269|PubMed:26164367, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:27516456}. Note=The disease is caused by variants affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4.

Disease: Long QT syndrome 14 (LQT14) [MIM:616247]: A 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. {ECO:0000269|PubMed:23388215, ECO:0000269|PubMed:24076290, ECO:0000269|PubMed:25036739, ECO:0000269|PubMed:26164367, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:28158429, ECO:0000269|PubMed:31454269}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: This protein has four functional calcium-binding sites. {ECO:0000269|PubMed:1474585, ECO:0000269|PubMed:27564677}.

Similarity: Belongs to the calmodulin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endomplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335). {ECO:0000269\|PubMed:16760425, ECO:0000269\|PubMed:23893133, ECO:0000269\|PubMed:26969752, ECO:0000269\|PubMed:27165696, ECO:0000269\|PubMed:28890335, ECO:0000269\|PubMed:31454269}.



Function:		(Microbial infection) Required for Legionella pneumophila SidJ glutamylase activity. {ECO:0000269\|PubMed:31330532}.


Subunit:		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 in the proper assembly of a functional heterotetrameric M channel (PubMed:27564677). Interacts with alpha-synuclein/SNCA (PubMed:23607618). Interacts with SLC9A1 in a calcium-dependent manner (PubMed:30287853). In the absence of Ca(+2), interacts with GIMAP4 (via IQ domain) (By similarity). Interacts with SCN8A; the interaction modulates the inactivation rate of SCN8A (By similarity). Interaction with KIF1A; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility (PubMed:30021165). Interacts with KCNN3 (PubMed:31155282). Interacts with KCNQ1 (via C-terminus); forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (PubMed:18165683,PubMed:25441029). Interacts with PIK3C3; the interaction modulates PIK3C3 kinase activity (PubMed:28890335). {ECO:0000250\|UniProtKB:P0DP26, ECO:0000250\|UniProtKB:P62157, ECO:0000250\|UniProtKB:P62161, ECO:0000250\|UniProtKB:P62204, ECO:0000269\|PubMed:12485993, ECO:0000269\|PubMed:12577052, ECO:0000269\|PubMed:12871148, ECO:0000269\|PubMed:15719022, ECO:0000269\|PubMed:15746192, ECO:0000269\|PubMed:16127172, ECO:0000269\|PubMed:16299511, ECO:0000269\|PubMed:16760425, ECO:0000269\|PubMed:17719545, ECO:0000269\|PubMed:18165683, ECO:0000269\|PubMed:18650434, ECO:0000269\|PubMed:20466722, ECO:0000269\|PubMed:21167176, ECO:0000269\|PubMed:22484487, ECO:0000269\|PubMed:23109337, ECO:0000269\|PubMed:23607618, ECO:0000269\|PubMed:23893133, ECO:0000269\|PubMed:25441029, ECO:0000269\|PubMed:26164367, ECO:0000269\|PubMed:27516456, ECO:0000269\|PubMed:27564677, ECO:0000269\|PubMed:27876793, ECO:0000269\|PubMed:28890335, ECO:0000269\|PubMed:30021165, ECO:0000269\|PubMed:30287853, ECO:0000269\|PubMed:31155282, ECO:0000269\|PubMed:9804419}.
Subunit:		(Microbial infection) Interacts with Rubella virus protease/methyltransferase p150. {ECO:0000269\|PubMed:20086014}.
Subunit:		(Microbial infection) Interacts with Legionella pneumophila glutamylase SidJ. {ECO:0000269\|PubMed:31330532}.
Subcellular location:		Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:16760425}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269\|PubMed:16760425}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:14654843}. Note=Distributed throughout the cell during interphase, but during mitosis becomes dramatically localized to the spindle poles and the spindle microtubules.
Domain:		The N-terminal and C-terminal lobes of CALM bind to the C- terminus of KCNQ1 in a clamp-like conformation. Binding of CALM C- terminus to KCNQ1 is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to KCNQ1 is calcium- dependent and regulates electrophysiological activity of the channel. {ECO:0000269\|PubMed:25441029}.
Ptm:		Ubiquitination results in a strongly decreased activity. {ECO:0000250}.
Ptm:		Phosphorylation results in a decreased activity. {ECO:0000250}.
Disease:		Ventricular tachycardia, catecholaminergic polymorphic, 4 (CPVT4) [MIM:614916]: 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. CPVT4 inheritance is autosomal dominant. {ECO:0000269\|PubMed:23040497, ECO:0000269\|PubMed:26164367, ECO:0000269\|PubMed:27165696, ECO:0000269\|PubMed:27516456}. Note=The disease is caused by variants affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4.
Disease:		Long QT syndrome 14 (LQT14) [MIM:616247]: A 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. {ECO:0000269\|PubMed:23388215, ECO:0000269\|PubMed:24076290, ECO:0000269\|PubMed:25036739, ECO:0000269\|PubMed:26164367, ECO:0000269\|PubMed:26969752, ECO:0000269\|PubMed:27165696, ECO:0000269\|PubMed:28158429, ECO:0000269\|PubMed:31454269}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		This protein has four functional calcium-binding sites. {ECO:0000269\|PubMed:1474585, ECO:0000269\|PubMed:27564677}.
Similarity:		Belongs to the calmodulin family. {ECO:0000305}.