Apoptosis Database

Description [+]

Synonyms: CALR, CALREGULIN,CRP55,HACBP,ERP60
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
Short gene description: Calreticulin Precursor (CRP55)(Calregulin)(HACBP)(ERp60) [Source:UniProtKB/Swiss-Prot;Acc:P14211]
Family: other
Process: apoptosis,
Pathways: apoptotic cell clearance,
Criteria: manually curated
Curator comment: Null
Human ortholog(s): CALR
WIKI: CALR-M_musculus

References [+]

Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM
Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where don't eat me signals are rendered inactive and eat me signals, including calreticulin and phosphatidylserine, congregate together and signal for removal. Cell. 2005 Oct 21;123(2):321-34.

Calreticulin is essential for cardiac development.
Mesaeli N, Nakamura K, Zvaritch E, Dickie P, Dziak E, Krause KH, Opas M, MacLennan DH, Michalak M
Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt-/- cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway. J Cell Biol. 1999 Mar 8;144(5):857-68.

References from Human ortholog(s):

Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM
Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where don't eat me signals are rendered inactive and eat me signals, including calreticulin and phosphatidylserine, congregate together and signal for removal. Cell. 2005 Oct 21;123(2):321-34.

Apoptosis: controlled demolition at the cellular level.
Taylor RC, Cullen SP, Martin SJ
Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses. Much of what happens during the demolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases. These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules. Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	Calreticulin	21	232

Evolution [+]

View protein alignment and tree with Jalview:

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Homologs list [+]

Name	Relationship	Species
A_aegypti_AAEL011773-PA	orthology	Aedes
A_aegypti_AAEL001005-PA	orthology	Aedes
A_gambiae_AGAP004212-PA	orthology	Anopheles
XR_024426.1	orthology	Chimpanzee
NA	orthology	Ciona
CALR_BOVIN	orthology	Cow
CALR	orthology	Dog
Crc	orthology	Fly
CALR	orthology	Gorilla
CALR	orthology	Horse
CALR	orthology	Human
CALR	orthology	Lyzard
CALR	orthology	Macaca
CALR	orthology	Monodelphis
CALR	orthology	Orangutan
CALR	orthology	Ornithorhynchus
CALR_RAT	orthology	Rat
crt-1	orthology	Worm
calr	orthology	Xenopus
CNE1	orthology	Yeast
A_aegypti_AAEL015100-PA	paralogy	Aedes
A_gambiae_AGAP005032-PA	paralogy	Anopheles
NP_001025791.1	paralogy	Chicken
IPI00597616.2	paralogy	Chicken
IPI00580922.2	paralogy	Chicken
CANX	paralogy	Chimpanzee
XR_022389.1	paralogy	Chimpanzee
CLGN	paralogy	Chimpanzee
NA	paralogy	Ciona
IPI00716596.5	paralogy	Cow
CLGN_BOVIN	paralogy	Cow
CALR3_BOVIN	paralogy	Cow
CLGN	paralogy	Dog
CALX_CANFA	paralogy	Dog
CALR3	paralogy	Dog
CG9906	paralogy	Fly
Cnx99A	paralogy	Fly
CG1924	paralogy	Fly
CALR3	paralogy	Fugu
CLGN	paralogy	Fugu
CALR	paralogy	Fugu
CANX	paralogy	Fugu
CLGN	paralogy	Gasterosteus
CALR	paralogy	Gasterosteus
CANX	paralogy	Gasterosteus
CALR3 (1 of 2)	paralogy	Gasterosteus
CALR3 (2 of 2)	paralogy	Gasterosteus
CANX	paralogy	Gorilla
XP_001494051.2	paralogy	Horse
CALR3	paralogy	Horse
CLGN	paralogy	Horse
CANX	paralogy	Horse
CALR3	paralogy	Human
CANX	paralogy	Human
CLGN	paralogy	Human
CANX	paralogy	Lyzard
CLGN	paralogy	Lyzard
CANX	paralogy	Macaca
M_mulatta_ENSMMUP00000040204	paralogy	Macaca
CLGN	paralogy	Macaca
CLGN	paralogy	Medaka
CALR3 (2 of 2)	paralogy	Medaka
CALR	paralogy	Medaka
CANX	paralogy	Medaka
CALR3 (1 of 2)	paralogy	Medaka
XR_030339.1	paralogy	Monodelphis
M_domestica_ENSMODP00000020352	paralogy	Monodelphis
M_domestica_ENSMODP00000019327	paralogy	Monodelphis
CLGN	paralogy	Monodelphis
XM_001372298.1	paralogy	Monodelphis
CALR3	paralogy	Monodelphis
Calr4	paralogy	Mouse
Canx	paralogy	Mouse
Clgn	paralogy	Mouse
Calr3	paralogy	Mouse
CANX	paralogy	Orangutan
CLGN	paralogy	Orangutan
CALR3	paralogy	Orangutan
O_anatinus_ENSOANP00000023446	paralogy	Ornithorhynchus
CLGN	paralogy	Ornithorhynchus
CANX	paralogy	Ornithorhynchus
CALR3	paralogy	Ornithorhynchus
CANX	paralogy	Rabbit
CALR3	paralogy	Rabbit
CLGN	paralogy	Rabbit
NP_001012212.1	paralogy	Rat
CALX_RAT	paralogy	Rat
Calr4	paralogy	Rat
NP_001102942.1	paralogy	Rat
CANX (1 of 2)	paralogy	Tetraodon
CALR	paralogy	Tetraodon
CLGN	paralogy	Tetraodon
CANX (2 of 2)	paralogy	Tetraodon
cnx-1	paralogy	Worm
canx	paralogy	Xenopus
CALR3	paralogy	Xenopus
CLGN	paralogy	Xenopus
CLGN	paralogy	Zebra finch
CANX	paralogy	Zebra finch
CALR (1 of 3)	paralogy	Zebrafish
CANX (2 of 2)	paralogy	Zebrafish
canx	paralogy	Zebrafish
clgn	paralogy	Zebrafish
calrl	paralogy	Zebrafish
calr	paralogy	Zebrafish

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Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0002502	peptide antigen assembly with MHC class I protein complex	biological_proccess	IMP
GO:0006457	protein folding	biological_proccess	IEA
GO:0010149	senescence	biological_proccess	IMP
GO:0030866	cortical actin cytoskeleton organization	biological_proccess	IDA
GO:0040020	regulation of meiosis	biological_proccess	IDA
GO:0045787	positive regulation of cell cycle	biological_proccess	IMP
GO:0050766	positive regulation of phagocytosis	biological_proccess	IMP
GO:0008284	positive regulation of cell proliferation	biological_proccess	IEA
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological_proccess	IEA
GO:0007050	cell cycle arrest	biological_proccess	IEA
GO:0006611	protein export from nucleus	biological_proccess	IEA
GO:0045740	positive regulation of DNA replication	biological_proccess	IEA
GO:0033144	negative regulation of steroid hormone receptor signaling pathway	biological_proccess	IEA
GO:0045665	negative regulation of neuron differentiation	biological_proccess	IEA
GO:0048387	negative regulation of retinoic acid receptor signaling pathway	biological_proccess	IEA
GO:0010149	senescence	biological_proccess	IEA
GO:0045787	positive regulation of cell cycle	biological_proccess	IEA
GO:0017148	negative regulation of translation	biological_proccess	IEA
GO:0003729	mRNA binding	mollecular_function	IDA
GO:0005509	calcium ion binding	mollecular_function	IDA
GO:0005529	sugar binding	mollecular_function	IEA
GO:0008270	zinc ion binding	mollecular_function	IEA
GO:0051082	unfolded protein binding	mollecular_function	IEA
GO:0046872	metal ion binding	mollecular_function	IEA
GO:0016564	transcription repressor activity	mollecular_function	IEA
GO:0005178	integrin binding	mollecular_function	IEA
GO:0050681	androgen receptor binding	mollecular_function	IEA
GO:0003729	mRNA binding	mollecular_function	IEA
GO:0008937	ferredoxin reductase activity	mollecular_function	IEA
GO:0005615	extracellular space	cell_component	IDA
GO:0005783	endoplasmic reticulum	cell_component	IDA
GO:0005788	endoplasmic reticulum lumen	cell_component	IEA
GO:0005792	microsome	cell_component	IDA
GO:0005844	polysome	cell_component	IDA
GO:0009897	external side of plasma membrane	cell_component	IDA
GO:0042824	MHC class I peptide loading complex	cell_component	IMP
GO:0005634	nucleus	cell_component	IEA
GO:0005829	cytosol	cell_component	IEA
GO:0048471	perinuclear region of cytoplasm	cell_component	IEA
GO:0005783	endoplasmic reticulum	cell_component	IEA

Check GO Evidence Codes here

Information from other databases [+]

CALR (Mus musculus)