P27797 · CALR_HUMAN

  • Protein
    Calreticulin
  • Gene
    CALR
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 (PubMed:7876246).
Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926).
Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity).
Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity).

Caution

Was originally thought to be the 52 kDa Ro autoantigen.

Features

Showing features for binding site.

141750100150200250300350400
TypeIDPosition(s)Description
Binding site26Ca2+ (UniProtKB | ChEBI)
Binding site62Ca2+ (UniProtKB | ChEBI)
Binding site64Ca2+ (UniProtKB | ChEBI)
Binding site109an alpha-D-glucoside (UniProtKB | ChEBI)
Binding site111an alpha-D-glucoside (UniProtKB | ChEBI)
Binding site128an alpha-D-glucoside (UniProtKB | ChEBI)
Binding site135an alpha-D-glucoside (UniProtKB | ChEBI)
Binding site317an alpha-D-glucoside (UniProtKB | ChEBI)
Binding site328Ca2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentacrosomal vesicle
Cellular Componentcell surface
Cellular Componentcollagen-containing extracellular matrix
Cellular Componentcortical granule
Cellular Componentcytolytic granule
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentendocytic vesicle lumen
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum lumen
Cellular Componentendoplasmic reticulum membrane
Cellular Componentendoplasmic reticulum quality control compartment
Cellular Componentendoplasmic reticulum-Golgi intermediate compartment membrane
Cellular Componentexternal side of plasma membrane
Cellular Componentextracellular exosome
Cellular Componentextracellular region
Cellular Componentextracellular space
Cellular Componentfocal adhesion
Cellular Componentlumenal side of endoplasmic reticulum membrane
Cellular Componentmembrane
Cellular ComponentMHC class I peptide loading complex
Cellular Componentnuclear envelope
Cellular Componentnucleus
Cellular Componentperinuclear region of cytoplasm
Cellular Componentphagocytic vesicle membrane
Cellular Componentribosome
Cellular Componentsarcoplasmic reticulum lumen
Cellular Componentsmooth endoplasmic reticulum
Molecular Functioncalcium ion binding
Molecular Functioncarbohydrate binding
Molecular Functioncomplement component C1q complex binding
Molecular FunctionDNA binding
Molecular Functionhormone binding
Molecular Functionintegrin binding
Molecular Functioniron ion binding
Molecular Functionmolecular sequestering activity
Molecular FunctionmRNA binding
Molecular Functionnuclear androgen receptor binding
Molecular Functionnuclear export signal receptor activity
Molecular Functionpeptide binding
Molecular Functionprotein folding chaperone
Molecular Functionprotein-folding chaperone binding
Molecular FunctionRNA binding
Molecular Functionubiquitin protein ligase binding
Molecular Functionunfolded protein binding
Molecular Functionzinc ion binding
Biological Processcardiac muscle cell differentiation
Biological Processcellular response to electrical stimulus
Biological Processcellular response to lithium ion
Biological Processcellular response to virus
Biological Processcellular senescence
Biological Processcortical actin cytoskeleton organization
Biological ProcessERAD pathway
Biological Processintracellular calcium ion homeostasis
Biological Processnegative regulation of DNA-templated transcription
Biological Processnegative regulation of intracellular steroid hormone receptor signaling pathway
Biological Processnegative regulation of neuron differentiation
Biological Processnegative regulation of retinoic acid receptor signaling pathway
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processnegative regulation of translation
Biological Processnegative regulation of trophoblast cell migration
Biological Processnuclear receptor-mediated glucocorticoid signaling pathway
Biological Processpeptide antigen assembly with MHC class I protein complex
Biological Processpositive regulation of cell cycle
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of dendritic cell chemotaxis
Biological Processpositive regulation of endothelial cell migration
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of non-canonical NF-kappaB signal transduction
Biological Processpositive regulation of phagocytosis
Biological Processpositive regulation of substrate adhesion-dependent cell spreading
Biological Processprotein export from nucleus
Biological Processprotein folding
Biological Processprotein folding in endoplasmic reticulum
Biological Processprotein localization to nucleus
Biological Processprotein maturation by protein folding
Biological Processprotein stabilization
Biological Processregulation of apoptotic process
Biological Processregulation of DNA-templated transcription
Biological Processregulation of meiotic nuclear division
Biological Processresponse to estradiol
Biological Processresponse to glycoside
Biological Processresponse to testosterone
Biological Processresponse to xenobiotic stimulus
Biological Processsequestering of calcium ion
Biological Processspermatogenesis

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Calreticulin
  • Alternative names
    • CRP55
    • Calregulin
    • Endoplasmic reticulum resident protein 60 (ERp60)
    • HACBP
    • grp60

Gene names

    • Name
      CALR
    • Synonyms
      CRTC

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P27797
  • Secondary accessions
    • Q6IAT4
    • Q9UDG2

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm, cytosol
Cell surface
Cytolytic granule
Note: Also found in cell surface (T cells), cytosol and extracellular matrix (PubMed:10358038).
During oocyte maturation and after parthenogenetic activation accumulates in cortical granules. In pronuclear and early cleaved embryos localizes weakly to cytoplasm around nucleus and more strongly in the region near the cortex (By similarity).
In cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation (By similarity).

Keywords

Disease & Variants

Involvement in disease

  • CALR somatic mutations are frequently found in myeloproliferative neoplasms lacking JAK2 or MPL mutations. Myeloproliferative neoplasms are chronic myeloid cancers characterized by overproduction of mature blood cells, and may evolve into acute myeloid leukemia. In addition to chronic myeloid leukemia with the BCR-ABL fusion gene, the three most common myeloproliferative neoplasms are essential thrombocythemia, polycythemia vera, and myelofibrosis

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 440 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for signal, chain, modified residue, disulfide bond, modified residue (large scale data), glycosylation.

TypeIDPosition(s)SourceDescription
Signal1-17UniProt
ChainPRO_000000417318-417UniProtCalreticulin
Modified residue48UniProtN6-acetyllysine
Modified residue64UniProtN6-(2-hydroxyisobutyryl)lysine
Disulfide bond105↔137UniProt
Modified residue159UniProtN6-acetyllysine
Modified residue (large scale data)193PRIDEPhosphoserine
Modified residue (large scale data)195PRIDEPhosphoserine
Modified residue209UniProtN6-acetyllysine
Modified residue (large scale data)214PRIDEPhosphoserine
Modified residue (large scale data)231PRIDEPhosphoserine
Modified residue (large scale data)285PRIDEPhosphotyrosine
Glycosylation344UniProtN-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

2D gel databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

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).
Interacts with CLCC1 (PubMed:30157172).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P27797APP P050675EBI-1049597, EBI-77613
BINARY P27797ARHGEF28 Q8N1W1-43EBI-1049597, EBI-13062134
BINARY P27797C1orf216 Q8TAB53EBI-1049597, EBI-747505
BINARY P27797CAMTA2 O94983-53EBI-1049597, EBI-10176008
BINARY P27797CNOT3 O751753EBI-1049597, EBI-743073
BINARY P27797CRELD2 Q6UXH1-23EBI-1049597, EBI-21670927
BINARY P27797DNASE1L1 P491843EBI-1049597, EBI-20894690
BINARY P27797DRC7 Q8IY823EBI-1049597, EBI-10262896
BINARY P27797EGFL8 Q999443EBI-1049597, EBI-3924130
BINARY P27797EPCAM P164223EBI-1049597, EBI-1171184
BINARY P27797EVA1B Q9NVM13EBI-1049597, EBI-10314666
BINARY P27797FAHD2A Q96GK73EBI-1049597, EBI-21647872
BINARY P27797FUT2 Q109813EBI-1049597, EBI-9090702
BINARY P27797GABARAP O951664EBI-1049597, EBI-712001
BINARY P27797GJA5 P363823EBI-1049597, EBI-750433
BINARY P27797GNAO1 P094713EBI-1049597, EBI-715087
BINARY P27797GSC2 O154993EBI-1049597, EBI-19954058
BINARY P27797HLA-DRB3 P794833EBI-1049597, EBI-3910269
BINARY P27797HSD3B1 P140603EBI-1049597, EBI-17426018
BINARY P27797HSPB1 P047922EBI-1049597, EBI-352682
BINARY P27797HUWE1 Q7Z6Z7-23EBI-1049597, EBI-10975491
BINARY P27797IDH1 O758743EBI-1049597, EBI-715695
BINARY P27797ISY1 Q9ULR03EBI-1049597, EBI-2557660
BINARY P27797KIAA1683 A0JP073EBI-1049597, EBI-10171456
BINARY P27797KLRC1 P267153EBI-1049597, EBI-9018187
BINARY P27797LEG1 Q6P5S23EBI-1049597, EBI-11750531
BINARY P27797LGALS1 P093823EBI-1049597, EBI-1048875
BINARY P27797LGALS8 O00214-23EBI-1049597, EBI-12069522
BINARY P27797MAGEA2B P433563EBI-1049597, EBI-5650739
BINARY P27797MAVS Q7Z4343EBI-1049597, EBI-995373
BINARY P27797MBL2 P112266EBI-1049597, EBI-5325353
BINARY P27797MFI Q8NCR33EBI-1049597, EBI-744790
BINARY P27797MGC39372 Q8TB023EBI-1049597, EBI-25834188
BINARY P27797MMAB Q96EY83EBI-1049597, EBI-7825413
BINARY P27797MTNR1A P480393EBI-1049597, EBI-1188238
BINARY P27797MYBPHL A2RUH73EBI-1049597, EBI-9088235
BINARY P27797MYNN Q9NPC73EBI-1049597, EBI-3446748
BINARY P27797NEK6 Q9HC98-43EBI-1049597, EBI-11750983
BINARY P27797NFATC2IP Q8NCF5-23EBI-1049597, EBI-12305293
BINARY P27797NLRP3 Q96P203EBI-1049597, EBI-6253230
BINARY P27797NXPE1 Q8N3233EBI-1049597, EBI-25834085
BINARY P27797PABIR3 Q6P4D5-23EBI-1049597, EBI-9091052
BINARY P27797PIAS4 Q8N2W93EBI-1049597, EBI-473160
BINARY P27797POC1A Q8NBT03EBI-1049597, EBI-2557132
BINARY P27797PPEF1 O148293EBI-1049597, EBI-2931238
BINARY P27797PRAM1 Q96QH23EBI-1049597, EBI-2860740
BINARY P27797PSAT1 Q9Y6173EBI-1049597, EBI-709652
BINARY P27797PSMC4 P436863EBI-1049597, EBI-743997
BINARY P27797PSMD2 Q132003EBI-1049597, EBI-357648
BINARY P27797PYGO1 Q9Y3Y43EBI-1049597, EBI-3397474
BINARY P27797 Q9BQ293EBI-1049597, EBI-22013570
BINARY P27797RAB31 Q136363EBI-1049597, EBI-725987
BINARY P27797RAB3C Q96E173EBI-1049597, EBI-4287022
BINARY P27797RAP1B P612243EBI-1049597, EBI-358143
BINARY P27797RASSF2 P507493EBI-1049597, EBI-960081
BINARY P27797RBM17 Q96I253EBI-1049597, EBI-740272
BINARY P27797RBM5 P527563EBI-1049597, EBI-714003
BINARY P27797SGTB Q96EQ03EBI-1049597, EBI-744081
BINARY P27797SLC25A11 Q029783EBI-1049597, EBI-359174
BINARY P27797SMARCB1 Q128245EBI-1049597, EBI-358419
BINARY P27797SP6 Q3SY563EBI-1049597, EBI-11175533
BINARY P27797SPATA17 Q96L033EBI-1049597, EBI-13322423
BINARY P27797SPRED2 Q7Z6983EBI-1049597, EBI-7082156
BINARY P27797TAF1B Q53T943EBI-1049597, EBI-1560239
BINARY P27797TAFAZZIN F6Y2X33EBI-1049597, EBI-25833693
BINARY P27797TAP1 Q035182EBI-1049597, EBI-747259
BINARY P27797TDO2 P487753EBI-1049597, EBI-743494
BINARY P27797THAP7 Q9BT493EBI-1049597, EBI-741350
BINARY P27797THBS3 P497463EBI-1049597, EBI-2530931
BINARY P27797TMX3 Q96JJ7-23EBI-1049597, EBI-25833898
BINARY P27797TNMD Q9H2S6-23EBI-1049597, EBI-12003398
BINARY P27797TPGS2 Q68CL5-33EBI-1049597, EBI-9091010
BINARY P27797TPX2 Q9ULW03EBI-1049597, EBI-1037322
BINARY P27797TRNAU1AP Q9NX073EBI-1049597, EBI-12581310
BINARY P27797TUBB P074373EBI-1049597, EBI-350864
BINARY P27797U2AF1 Q7Z7803EBI-1049597, EBI-25833730
BINARY P27797USP12 O753173EBI-1049597, EBI-2511507
BINARY P27797ZHX1-C8orf76 Q96EF93EBI-1049597, EBI-25830993

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, repeat, compositional bias, motif.

TypeIDPosition(s)Description
Region18-197N-domain
Repeat191-2021-1
Region191-2554 X approximate repeats
Region193-278Disordered
Region198-308P-domain
Compositional bias199-254Basic and acidic residues
Repeat210-2211-2
Repeat227-2381-3
Region237-270Interaction with PPIB
Repeat244-2551-4
Repeat259-2692-1
Region259-2973 X approximate repeats
Repeat273-2832-2
Repeat287-2972-3
Region309-417C-domain
Region350-417Disordered
Compositional bias352-381Basic and acidic residues
Compositional bias382-417Acidic residues
Motif414-417Prevents secretion from ER

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.

Sequence similarities

Belongs to the calreticulin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    417
  • Mass (Da)
    48,142
  • Last updated
    1992-08-01 v1
  • Checksum
    BC37C3C0F1054FB2
MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSRWIESKHKSDFGKFVLSSGKFYGDEEKDKGLQTSQDARFYALSASFEPFSNKGQTLVVQFTVKHEQNIDCGGGYVKLFPNSLDQTDMHGDSEYNIMFGPDICGPGTKKVHVIFNYKGKNVLINKDIRCKDDEFTHLYTLIVRPDNTYEVKIDNSQVESGSLEDDWDFLPPKKIKDPDASKPEDWDERAKIDDPTDSKPEDWDKPEHIPDPDAKKPEDWDEEMDGEWEPPVIQNPEYKGEWKPRQIDNPDYKGTWIHPEIDNPEYSPDPSIYAYDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETWGVTKAAEKQMKDKQDEEQRLKEEEEDKKRKEEEEAEDKEDDEDKDEDEEDEEDKEEDEEEDVPGQAKDEL

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
K7EJB9K7EJB9_HUMANCALR349
A0A7P0T861A0A7P0T861_HUMANCALR356
K7ELE2K7ELE2_HUMANCALR13
K7EL50K7EL50_HUMANCALR378

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias199-254Basic and acidic residues
Compositional bias352-381Basic and acidic residues
Compositional bias382-417Acidic residues

Mass Spectrometry

Molecular mass is 46,879 Da. Determined by MALDI.

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M32294
EMBL· GenBank· DDBJ
AAA36582.1
EMBL· GenBank· DDBJ
mRNA
M84739
EMBL· GenBank· DDBJ
AAA51916.1
EMBL· GenBank· DDBJ
mRNA
AY047586
EMBL· GenBank· DDBJ
AAL13126.1
EMBL· GenBank· DDBJ
mRNA
AB451408
EMBL· GenBank· DDBJ
BAG70222.1
EMBL· GenBank· DDBJ
mRNA
BT007448
EMBL· GenBank· DDBJ
AAP36116.1
EMBL· GenBank· DDBJ
mRNA
CR457070
EMBL· GenBank· DDBJ
CAG33351.1
EMBL· GenBank· DDBJ
mRNA
AD000092
EMBL· GenBank· DDBJ
AAB51176.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471106
EMBL· GenBank· DDBJ
EAW84331.1
EMBL· GenBank· DDBJ
Genomic DNA
BC002500
EMBL· GenBank· DDBJ
AAH02500.1
EMBL· GenBank· DDBJ
mRNA
BC007911
EMBL· GenBank· DDBJ
AAH07911.1
EMBL· GenBank· DDBJ
mRNA
BC020493
EMBL· GenBank· DDBJ
AAH20493.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any 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. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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