======= CALR =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CALR
  * **<color #00a2e8>Official Name</color>**: calreticulin
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=811|811]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P27797|P27797]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CALR&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CALR|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/109091|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  Calreticulin is a multifunctional protein that acts as a major Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin binds to the synthetic peptide KLGFFKR, which is almost identical to an amino acid sequence in the DNA-binding domain of the superfamily of nuclear receptors. Calreticulin binds to antibodies in certain sera of systemic lupus and Sjogren patients which contain anti-Ro/SSA antibodies, it is highly conserved among species, and it is located in the endoplasmic and sarcoplasmic reticulum where it may bind calcium. The amino terminus of calreticulin interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. Calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element and can inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Thus, calreticulin can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen but this was later disproven. Increased autoantibody titer against human calreticulin is found in infants with complete congenital heart block of both the IgG and IgM classes. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). {ECO:0000250, ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:7876246}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Calreticulin|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|MHC class I protein complex assembly|
|peptide antigen assembly with MHC class I protein complex|
|sequestering of calcium ion|
|negative regulation of trophoblast cell migration|
|peptide antigen assembly with MHC protein complex|
|vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane|
|MHC class I peptide loading complex|
|MHC protein complex assembly|
|glucocorticoid receptor signaling pathway|
|corticosteroid receptor signaling pathway|
|complement component C1q binding|
|positive regulation of dendritic cell chemotaxis|
|negative regulation of retinoic acid receptor signaling pathway|
|sarcoplasmic reticulum lumen|
|ATF6-mediated unfolded protein response|
|protein maturation by protein folding|
|regulation of dendritic cell chemotaxis|
|regulation of trophoblast cell migration|
|hormone binding|
|cellular response to lithium ion|
|endocytic vesicle lumen|
|regulation of retinoic acid receptor signaling pathway|
|protein folding in endoplasmic reticulum|
|response to lithium ion|
|negative regulation of cell cycle arrest|
|protein folding chaperone|
|endoplasmic reticulum quality control compartment|
|smooth endoplasmic reticulum|
|integral component of lumenal side of endoplasmic reticulum membrane|
|regulation of meiotic nuclear division|
|cellular senescence|
|ER-nucleus signaling pathway|
|negative regulation of intracellular steroid hormone receptor signaling pathway|
|positive regulation of substrate adhesion-dependent cell spreading|
|response to testosterone|
|cortical actin cytoskeleton organization|
|polysome|
|androgen receptor binding|
|cortical cytoskeleton organization|
|regulation of meiotic cell cycle|
|peptide binding|
|regulation of substrate adhesion-dependent cell spreading|
|negative regulation of reproductive process|
|cell aging|
|intracellular steroid hormone receptor signaling pathway|
|positive regulation of phagocytosis|
|endoplasmic reticulum-Golgi intermediate compartment membrane|
|vesicle fusion|
|phagocytic vesicle membrane|
|antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent|
|positive regulation of NIK/NF-kappaB signaling|
|organelle membrane fusion|
|regulation of intracellular steroid hormone receptor signaling pathway|
|antigen processing and presentation of exogenous peptide antigen via MHC class I|
|acrosomal vesicle|
|positive regulation of leukocyte chemotaxis|
|cardiac muscle cell differentiation|
|regulation of phagocytosis|
|organelle fusion|
|antigen processing and presentation of peptide antigen via MHC class I|
|positive regulation of endothelial cell migration|
|chaperone binding|
|endoplasmic reticulum unfolded protein response|
|regulation of cell cycle arrest|
|regulation of NIK/NF-kappaB signaling|
|regulation of leukocyte chemotaxis|
|cardiocyte differentiation|
|steroid hormone mediated signaling pathway|
|positive regulation of cell-substrate adhesion|
|cellular response to unfolded protein|
|positive regulation of leukocyte migration|
|negative regulation of translation|
|integrin binding|
|membrane fusion|
|unfolded protein binding|
|iron ion binding|
|positive regulation of chemotaxis|
|response to estradiol|
|positive regulation of epithelial cell migration|
|negative regulation of cellular amide metabolic process|
|protein export from nucleus|
|cellular response to topologically incorrect protein|
|positive regulation of cell morphogenesis involved in differentiation|
|regulation of endothelial cell migration|
|nuclear export|
|regulation of reproductive process|
|mRNA binding|
|cardiac muscle tissue development|
|protein localization to nucleus|
|response to unfolded protein|
|intracellular receptor signaling pathway|
|maintenance of location|
|hormone-mediated signaling pathway|
|carbohydrate binding|
|antigen processing and presentation of exogenous peptide antigen|
|protein stabilization|
|nuclear envelope|
|antigen processing and presentation of exogenous antigen|
|response to topologically incorrect protein|
|cellular response to steroid hormone stimulus|
|antigen processing and presentation of peptide antigen|
|regulation of nuclear division|
|cellular response to metal ion|
|response to ketone|
|regulation of leukocyte migration|
|striated muscle cell differentiation|
|regulation of cell-substrate adhesion|
|regulation of chemotaxis|
|negative regulation of multi-organism process|
|antigen processing and presentation|
|regulation of epithelial cell migration|
|cellular response to inorganic substance|
|negative regulation of neuron differentiation|
|protein maturation|
|protein folding|
|receptor-mediated endocytosis|
|muscle cell differentiation|
|response to endoplasmic reticulum stress|
|negative regulation of cell migration|
|nucleocytoplasmic transport|
|nuclear transport|
|negative regulation of cell motility|
|aging|
|striated muscle tissue development|
|regulation of protein stability|
|negative regulation of neurogenesis|
|ubiquitin protein ligase binding|
|muscle tissue development|
|vesicle organization|
|regulation of cell morphogenesis involved in differentiation|
|endoplasmic reticulum lumen|
|negative regulation of cellular component movement|
|negative regulation of nervous system development|
|negative regulation of locomotion|
|negative regulation of cell cycle process|
|response to steroid hormone|
|negative regulation of cell development|
|regulation of translation|
|collagen-containing extracellular matrix|
|response to metal ion|
|positive regulation of cell cycle|
|external side of plasma membrane|
|positive regulation of cell adhesion|
|regulation of cellular amide metabolic process|
|focal adhesion|
|cellular calcium ion homeostasis|
|calcium ion homeostasis|
|cellular divalent inorganic cation homeostasis|
|muscle structure development|
|regulation of cell morphogenesis|
|divalent inorganic cation homeostasis|
|actin cytoskeleton organization|
|positive regulation of cell migration|
|cellular response to lipid|
|positive regulation of cell motility|
|posttranscriptional regulation of gene expression|
|heart development|
|response to inorganic substance|
|positive regulation of cellular component movement|
|positive regulation of cell development|
|cellular response to organic cyclic compound|
|spermatogenesis|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|endocytosis|
|cellular metal ion homeostasis|
|male gamete generation|
|actin filament-based process|
|negative regulation of cell cycle|
|positive regulation of response to external stimulus|
|cellular response to hormone stimulus|
|cell surface|
|metal ion homeostasis|
|cellular cation homeostasis|
|cellular ion homeostasis|
|regulation of neuron differentiation|
|import into cell|
|regulation of cell adhesion|
|gamete generation|
|perinuclear region of cytoplasm|
|cation homeostasis|
|negative regulation of cell differentiation|
|inorganic ion homeostasis|
|calcium ion binding|
|protein localization to organelle|
|cellular chemical homeostasis|
|regulation of cell cycle process|
|regulation of multi-organism process|
|ion homeostasis|
|regulation of neurogenesis|
|multicellular organismal reproductive process|
|sexual reproduction|
|zinc ion binding|
|cellular protein-containing complex assembly|
|multicellular organism reproduction|
|regulation of cell migration|
|membrane organization|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|circulatory system development|
|cellular homeostasis|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|response to organic cyclic compound|
|regulation of nervous system development|
|regulation of cell development|
|endoplasmic reticulum membrane|
|negative regulation of developmental process|
|positive regulation of cell differentiation|
|regulation of locomotion|
|Golgi apparatus|
|positive regulation of transport|
|regulation of cellular component movement|
|intracellular protein transport|
|multi-organism reproductive process|
|endoplasmic reticulum|
|response to drug|
|positive regulation of intracellular signal transduction|
|negative regulation of cellular protein metabolic process|
|regulation of anatomical structure morphogenesis|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|chemical homeostasis|
|positive regulation of immune system process|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|reproductive process|
|reproduction|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|protein transport|
|negative regulation of cellular biosynthetic process|
|intracellular transport|
|generation of neurons|
|peptide transport|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|amide transport|
|cellular protein localization|
|extracellular space|
|cellular macromolecule localization|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|homeostatic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|cellular response to stress|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|tissue development|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|nitrogen compound transport|
|protein-containing complex subunit organization|
|regulation of transport|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of gene expression|
|membrane|
|gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp507|Monensin 0.3μM R08 exp507]]|-1.93|
|[[:results:exp501|Methotrexate 0.01μM R08 exp501]]|-1.82|
|[[:results:exp122|Golgicide-A 4μM R03 exp122]]|1.73|
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|1.74|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|1.82|
|[[:results:exp245|UM0011500 5μM R05 exp245]]|2|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|2.12|
|[[:results:exp78|Pterostilbene 16μM R02 exp78]]|2.18|
|[[:results:exp83|Trametinib 10μM R02 exp83]]|2.26|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.495|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 3390
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 10.26 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CALR Expression in NALM6 Cells: 10.26'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>