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 superf... See more...

Aliases for CALR Gene

Aliases for CALR Gene

  • Calreticulin 2 3 4 5
  • Sicca Syndrome Antigen A (Autoantigen Ro; Calreticulin) 2 3
  • Endoplasmic Reticulum Resident Protein 60 3 4
  • Calregulin 3 4
  • CRP55 3 4
  • ERp60 3 4
  • HACBP 3 4
  • Grp60 3 4
  • Epididymis Secretory Sperm Binding Protein Li 99n 3
  • Autoantigen Ro 2
  • HEL-S-99n 3
  • CC1qR 3
  • CRTC 4
  • CRT 3
  • SSA 3
  • RO 3

External Ids for CALR Gene

Previous GeneCards Identifiers for CALR Gene

  • GC19P013180
  • GC19P013272
  • GC19P012894
  • GC19P012910
  • GC19P013049
  • GC19P012621

Summaries for CALR Gene

Entrez Gene Summary for CALR Gene

  • 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]

CIViC Summary for CALR Gene

GeneCards Summary for CALR Gene

CALR (Calreticulin) is a Protein Coding gene. Diseases associated with CALR include Myelofibrosis and Thrombocythemia 1. Among its related pathways are Metabolism of proteins and Calnexin/calreticulin cycle. Gene Ontology (GO) annotations related to this gene include ubiquitin protein ligase binding. An important paralog of this gene is CALR3.

UniProtKB/Swiss-Prot Summary for CALR Gene

  • 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).

Gene Wiki entry for CALR Gene

Additional gene information for CALR Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CALR Gene

Genomics for CALR Gene

GeneHancer (GH) Regulatory Elements for CALR Gene

Promoters and enhancers for CALR Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CALR on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CALR

Top Transcription factor binding sites by QIAGEN in the CALR gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • CUTL1
  • Nkx2-5
  • p53

Genomic Locations for CALR Gene

Genomic Locations for CALR Gene
chr19:12,938,578-12,944,490
(GRCh38/hg38)
Size:
5,913 bases
Orientation:
Plus strand
chr19:13,049,392-13,055,304
(GRCh37/hg19)
Size:
5,913 bases
Orientation:
Plus strand

Genomic View for CALR Gene

Genes around CALR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CALR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CALR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CALR Gene

Proteins for CALR Gene

  • Protein details for CALR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P27797-CALR_HUMAN
    Recommended name:
    Calreticulin
    Protein Accession:
    P27797
    Secondary Accessions:
    • Q6IAT4
    • Q9UDG2

    Protein attributes for CALR Gene

    Size:
    417 amino acids
    Molecular mass:
    48142 Da
    Quaternary structure:
    • Monomer. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interacts with PDIA3/ERp57 and SPACA9 (By similarity). Interacts with TRIM21 (PubMed:8666824). Interacts with NR3C1 (PubMed:11149926). Interacts with PPIB (PubMed:20801878). Interacts (via P-domain) with PDIA5 (PubMed:23614004). Interacts with GABARAP (PubMed:19154346). Interacts with HLA-E-B2M and HLA-G-B2M complexes (PubMed:9427624, PubMed:9640257). Interacts with HLA-F (PubMed:10605026).

    Three dimensional structures from OCA and Proteopedia for CALR Gene

neXtProt entry for CALR Gene

Post-translational modifications for CALR Gene

  • Glycosylation at Asn344
  • Ubiquitination at Lys24, Lys48, Lys55, and Lys159
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for CALR Gene

Antibody Products

Protein Products

No data available for DME Specific Peptides for CALR Gene

Domains & Families for CALR Gene

Gene Families for CALR Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CALR Gene

Suggested Antigen Peptide Sequences for CALR Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58668, highly similar to Calreticulin (B4E2Y9_HUMAN)
  • grp60 (CALR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P27797

UniProtKB/Swiss-Prot:

CALR_HUMAN :
  • Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity.
  • Belongs to the calreticulin family.
Domain:
  • Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity.
  • The interaction with glycans occurs through a binding site in the globular lectin domain.
  • The zinc binding sites are localized to the N-domain.
  • Associates with PDIA3 through the tip of the extended arm formed by the P-domain.
Family:
  • Belongs to the calreticulin family.
genes like me logo Genes that share domains with CALR: view

Function for CALR Gene

Molecular function for CALR Gene

UniProtKB/Swiss-Prot Function:
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).
GENATLAS Biochemistry:
calreticulin,calcium binding protein of endoplasmic and sarcoplasmic reticulum,48kDa

Phenotypes From GWAS Catalog for CALR Gene

Gene Ontology (GO) - Molecular Function for CALR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001849 complement component C1q binding TAS 15474971
GO:0003677 DNA binding NAS 11149926
GO:0003723 RNA binding HDA 22658674
GO:0003729 mRNA binding IDA 14726956
GO:0005178 integrin binding IPI 1911778
genes like me logo Genes that share ontologies with CALR: view
genes like me logo Genes that share phenotypes with CALR: view

Human Phenotype Ontology for CALR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CALR Gene

MGI Knock Outs for CALR:

miRNA for CALR Gene

miRTarBase miRNAs that target CALR

Clone Products

  • Addgene plasmids for CALR

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CALR Gene

Localization for CALR Gene

Subcellular locations from UniProtKB/Swiss-Prot for CALR Gene

Endoplasmic reticulum lumen. Cytoplasm, cytosol. Secreted, extracellular space, extracellular matrix. Cell surface. Sarcoplasmic reticulum lumen. Note=Also found in cell surface (T cells), cytosol and extracellular matrix (PubMed:10358038). Associated with the lytic granules in the cytolytic T-lymphocytes. {ECO:0000269 PubMed:10358038, ECO:0000269 PubMed:8418194}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CALR gene
Compartment Confidence
extracellular 5
nucleus 5
endoplasmic reticulum 5
cytosol 5
plasma membrane 4
golgi apparatus 4
cytoskeleton 3
mitochondrion 3
lysosome 3
peroxisome 2
endosome 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CALR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001669 acrosomal vesicle IEA --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA,IMP 22377355
GO:0005623 cell IEA --
GO:0005634 nucleus IEA,IDA 8107809
genes like me logo Genes that share ontologies with CALR: view

Pathways & Interactions for CALR Gene

genes like me logo Genes that share pathways with CALR: view

Pathways by source for CALR Gene

2 GeneGo (Thomson Reuters) pathways for CALR Gene
  • Immune response Antigen presentation by MHC class I
  • Transcription_Role of VDR in regulation of genes involved in osteoporosis
2 Qiagen pathways for CALR Gene
  • Androgen Signaling
  • Presenilin-Mediated Signaling
2 Cell Signaling Technology pathways for CALR Gene

Gene Ontology (GO) - Biological Process for CALR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 8107809
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I TAS --
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent TAS --
GO:0002502 peptide antigen assembly with MHC class I protein complex ISS 11825569
GO:0006355 regulation of transcription, DNA-templated TAS 8107808
genes like me logo Genes that share ontologies with CALR: view

No data available for SIGNOR curated interactions for CALR Gene

Drugs & Compounds for CALR Gene

(52) Drugs for CALR Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Melatonin Approved, Vet_approved Nutra Antagonist, Full agonist, Agonist, Target Melatonin receptors MT inhibitor, Endogenous hormone; agonist at MT1 and MT2 374
Calcium Approved Nutra 7884
Antihemophilic factor, human recombinant Approved, Investigational Pharma Target, chaperone 0
Calcium Citrate Approved, Investigational Pharma Target, ligand 0
Calcium Phosphate Approved Pharma Target, ligand 0

(37) Additional Compounds for CALR Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CALR: view

Transcripts for CALR Gene

mRNA/cDNA for CALR Gene

1 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for CALR

Alternative Splicing Database (ASD) splice patterns (SP) for CALR Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b
SP1:
SP2: -
SP3:
SP4:

Relevant External Links for CALR Gene

GeneLoc Exon Structure for
CALR

Expression for CALR Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CALR Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CALR Gene



Protein tissue co-expression partners for CALR Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CALR

SOURCE GeneReport for Unigene cluster for CALR Gene:

Hs.515162

Evidence on tissue expression from TISSUES for CALR Gene

  • Skin(4.9)
  • Nervous system(4.9)
  • Eye(4.8)
  • Liver(4.8)
  • Pancreas(4.8)
  • Lung(4.7)
  • Intestine(4.4)
  • Kidney(4.1)
  • Spleen(3.7)
  • Blood(3.6)
  • Heart(3.6)
  • Muscle(3.4)
  • Stomach(3.4)
  • Bone marrow(3.3)
  • Lymph node(3.3)
  • Thyroid gland(3.1)
  • Bone(2.8)
  • Adrenal gland(2.5)
  • Gall bladder(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CALR Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeleton
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • heart
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • liver
  • spleen
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with CALR: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for CALR Gene

Orthologs for CALR Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CALR Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CALR 31 30
  • 99.9 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CALR 31 30
  • 90.61 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CALR 31 30
  • 89.56 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Calr 17 31 30
  • 88.21 (n)
rat
(Rattus norvegicus)
Mammalia Calr 30
  • 87.73 (n)
platypus
(Ornithorhynchus anatinus)