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Protein

Calreticulin

Gene

CALR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity2 Publications

Caution

Was originally thought to be the 52 kDa Ro autoantigen.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi26Calcium; via carbonyl oxygen1
Metal bindingi62Calcium; via carbonyl oxygen1
Metal bindingi64Calcium; via carbonyl oxygen1
Binding sitei109CarbohydrateBy similarity1
Binding sitei111CarbohydrateBy similarity1
Binding sitei128CarbohydrateBy similarity1
Binding sitei135CarbohydrateBy similarity1
Binding sitei317CarbohydrateBy similarity1
Metal bindingi328Calcium1

GO - Molecular functioni

  • androgen receptor binding Source: BHF-UCL
  • calcium ion binding Source: UniProtKB
  • carbohydrate binding Source: BHF-UCL
  • chaperone binding Source: BHF-UCL
  • complement component C1q binding Source: BHF-UCL
  • DNA binding Source: UniProtKB
  • hormone binding Source: Ensembl
  • integrin binding Source: BHF-UCL
  • iron ion binding Source: Ensembl
  • mRNA binding Source: BHF-UCL
  • peptide binding Source: Ensembl
  • protein binding involved in protein folding Source: BHF-UCL
  • RNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • unfolded protein binding Source: BHF-UCL
  • zinc ion binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionChaperone
LigandCalcium, Lectin, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-168316 Assembly of Viral Components at the Budding Site
R-HSA-3000480 Scavenging by Class A Receptors
R-HSA-3000484 Scavenging by Class F Receptors
R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-901042 Calnexin/calreticulin cycle
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC

Protein family/group databases

MoonProtiP27797
UniLectiniP27797

Names & Taxonomyi

Protein namesi
Recommended name:
Calreticulin
Alternative name(s):
CRP55
Calregulin
Endoplasmic reticulum resident protein 60
Short name:
ERp60
HACBP
grp60
Gene namesi
Name:CALR
Synonyms:CRTC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000179218.13
HGNCiHGNC:1455 CALR
MIMi109091 gene
neXtProtiNX_P27797

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Extracellular matrix, Sarcoplasmic reticulum, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi811
MalaCardsiCALR
OpenTargetsiENSG00000179218
Orphaneti3318 Essential thrombocythemia
824 Myelofibrosis with myeloid metaplasia
PharmGKBiPA26046

Chemistry databases

DrugBankiDB00025 Antihemophilic Factor (Recombinant)
DB01065 Melatonin
DB00031 Tenecteplase

Polymorphism and mutation databases

BioMutaiCALR
DMDMi117501

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Combined sources7 PublicationsAdd BLAST17
ChainiPRO_000000417318 – 417CalreticulinAdd BLAST400

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei48N6-acetyllysineCombined sources1
Disulfide bondi105 ↔ 1372 Publications
Modified residuei159N6-acetyllysineCombined sources1
Modified residuei209N6-acetyllysineCombined sources1
Glycosylationi344N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein

Proteomic databases

EPDiP27797
PaxDbiP27797
PeptideAtlasiP27797
PRIDEiP27797
ProteomicsDBi54410
TopDownProteomicsiP27797

2D gel databases

DOSAC-COBS-2DPAGEiP27797
OGPiP27797
REPRODUCTION-2DPAGEiIPI00020599
SWISS-2DPAGEiP27797
UCD-2DPAGEiP27797

PTM databases

GlyConnecti1060
iPTMnetiP27797
PhosphoSitePlusiP27797
SwissPalmiP27797

Expressioni

Gene expression databases

BgeeiENSG00000179218 Expressed in 236 organ(s), highest expression level in thyroid gland
CleanExiHS_CALR
ExpressionAtlasiP27797 baseline and differential
GenevisibleiP27797 HS

Organism-specific databases

HPAiCAB001513
CAB019952
HPA002242

Interactioni

Subunit structurei

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).By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107262, 145 interactors
CORUMiP27797
DIPiDIP-104N
IntActiP27797, 50 interactors
MINTiP27797
STRINGi9606.ENSP00000320866

Structurei

Secondary structure

1417
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00333
ProteinModelPortaliP27797
SMRiP27797
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27797

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati191 – 2021-1Add BLAST12
Repeati210 – 2211-2Add BLAST12
Repeati227 – 2381-3Add BLAST12
Repeati244 – 2551-4Add BLAST12
Repeati259 – 2692-1Add BLAST11
Repeati273 – 2832-2Add BLAST11
Repeati287 – 2972-3Add BLAST11

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni18 – 197N-domainAdd BLAST180
Regioni191 – 2554 X approximate repeatsAdd BLAST65
Regioni198 – 308P-domainAdd BLAST111
Regioni237 – 270Interaction with PPIBBy similarityAdd BLAST34
Regioni259 – 2973 X approximate repeatsAdd BLAST39
Regioni309 – 417C-domainAdd BLAST109

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi414 – 417Prevents secretion from ER4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi351 – 408Asp/Glu/Lys-richAdd BLAST58

Domaini

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 similaritiesi

Belongs to the calreticulin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG0674 Eukaryota
ENOG410XRR7 LUCA
GeneTreeiENSGT00430000030841
HOGENOMiHOG000192435
HOVERGENiHBG005407
InParanoidiP27797
KOiK08057
OMAiDTWIYSK
OrthoDBiEOG091G0AP1
PhylomeDBiP27797
TreeFamiTF338438

Family and domain databases

Gene3Di2.10.250.10, 1 hit
InterProiView protein in InterPro
IPR001580 Calret/calnex
IPR018124 Calret/calnex_CS
IPR009169 Calreticulin
IPR009033 Calreticulin/calnexin_P_dom_sf
IPR013320 ConA-like_dom_sf
PANTHERiPTHR11073 PTHR11073, 1 hit
PfamiView protein in Pfam
PF00262 Calreticulin, 2 hits
PIRSFiPIRSF002356 Calreticulin, 1 hit
PRINTSiPR00626 CALRETICULIN
SUPFAMiSSF49899 SSF49899, 1 hit
SSF63887 SSF63887, 1 hit
PROSITEiView protein in PROSITE
PS00803 CALRETICULIN_1, 1 hit
PS00804 CALRETICULIN_2, 1 hit
PS00805 CALRETICULIN_REPEAT, 3 hits
PS00014 ER_TARGET, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P27797-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLLSVPLLLG LLGLAVAEPA VYFKEQFLDG DGWTSRWIES KHKSDFGKFV
60 70 80 90 100
LSSGKFYGDE EKDKGLQTSQ DARFYALSAS FEPFSNKGQT LVVQFTVKHE
110 120 130 140 150
QNIDCGGGYV KLFPNSLDQT DMHGDSEYNI MFGPDICGPG TKKVHVIFNY
160 170 180 190 200
KGKNVLINKD IRCKDDEFTH LYTLIVRPDN TYEVKIDNSQ VESGSLEDDW
210 220 230 240 250
DFLPPKKIKD PDASKPEDWD ERAKIDDPTD SKPEDWDKPE HIPDPDAKKP
260 270 280 290 300
EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS
310 320 330 340 350
PDPSIYAYDN FGVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT
360 370 380 390 400
KAAEKQMKDK QDEEQRLKEE EEDKKRKEEE EAEDKEDDED KDEDEEDEED
410
KEEDEEEDVP GQAKDEL
Length:417
Mass (Da):48,142
Last modified:August 1, 1992 - v1
Checksum:iBC37C3C0F1054FB2
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EJB9K7EJB9_HUMAN
Calreticulin
CALR
247Annotation score:
K7EL50K7EL50_HUMAN
Calreticulin
CALR
163Annotation score:
K7ELE2K7ELE2_HUMAN
Calreticulin
CALR
13Annotation score:

Mass spectrometryi

Molecular mass is 46879 Da from positions 18 - 417. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32294 mRNA Translation: AAA36582.1
M84739 mRNA Translation: AAA51916.1
AY047586 mRNA Translation: AAL13126.1
AB451408 mRNA Translation: BAG70222.1
BT007448 mRNA Translation: AAP36116.1
CR457070 mRNA Translation: CAG33351.1
AD000092 Genomic DNA Translation: AAB51176.1
CH471106 Genomic DNA Translation: EAW84331.1
BC002500 mRNA Translation: AAH02500.1
BC007911 mRNA Translation: AAH07911.1
BC020493 mRNA Translation: AAH20493.1
CCDSiCCDS12288.1
PIRiA42330 A37047
RefSeqiNP_004334.1, NM_004343.3
UniGeneiHs.515162

Genome annotation databases

EnsembliENST00000316448; ENSP00000320866; ENSG00000179218
GeneIDi811
KEGGihsa:811

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Calreticulin entry

Functional Glycomics Gateway - Glycan Binding

Calreticulin

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32294 mRNA Translation: AAA36582.1
M84739 mRNA Translation: AAA51916.1
AY047586 mRNA Translation: AAL13126.1
AB451408 mRNA Translation: BAG70222.1
BT007448 mRNA Translation: AAP36116.1
CR457070 mRNA Translation: CAG33351.1
AD000092 Genomic DNA Translation: AAB51176.1
CH471106 Genomic DNA Translation: EAW84331.1
BC002500 mRNA Translation: AAH02500.1
BC007911 mRNA Translation: AAH07911.1
BC020493 mRNA Translation: AAH20493.1
CCDSiCCDS12288.1
PIRiA42330 A37047
RefSeqiNP_004334.1, NM_004343.3
UniGeneiHs.515162

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CLRX-ray2.00C/F1-10[»]
3DOWX-ray2.30B195-205[»]
3POSX-ray1.65A/B/C18-204[»]
A/B/C302-368[»]
3POWX-ray1.55A18-204[»]
A302-368[»]
5LK5X-ray2.30A/B/C/D/E/F/G/H/I/J18-204[»]
A/B/C/D/E/F/G/H/I/J303-368[»]
5V90X-ray3.25B/D238-273[»]
6ENYelectron microscopy5.80G18-417[»]
DisProtiDP00333
ProteinModelPortaliP27797
SMRiP27797
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107262, 145 interactors
CORUMiP27797
DIPiDIP-104N
IntActiP27797, 50 interactors
MINTiP27797
STRINGi9606.ENSP00000320866

Chemistry databases

DrugBankiDB00025 Antihemophilic Factor (Recombinant)
DB01065 Melatonin
DB00031 Tenecteplase

Protein family/group databases

MoonProtiP27797
UniLectiniP27797

PTM databases

GlyConnecti1060
iPTMnetiP27797
PhosphoSitePlusiP27797
SwissPalmiP27797

Polymorphism and mutation databases

BioMutaiCALR
DMDMi117501

2D gel databases

DOSAC-COBS-2DPAGEiP27797
OGPiP27797
REPRODUCTION-2DPAGEiIPI00020599
SWISS-2DPAGEiP27797
UCD-2DPAGEiP27797

Proteomic databases

EPDiP27797
PaxDbiP27797
PeptideAtlasiP27797
PRIDEiP27797
ProteomicsDBi54410
TopDownProteomicsiP27797

Protocols and materials databases

DNASUi811
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316448; ENSP00000320866; ENSG00000179218
GeneIDi811
KEGGihsa:811

Organism-specific databases

CTDi811
DisGeNETi811
EuPathDBiHostDB:ENSG00000179218.13
GeneCardsiCALR
HGNCiHGNC:1455 CALR
HPAiCAB001513
CAB019952
HPA002242
MalaCardsiCALR
MIMi109091 gene
neXtProtiNX_P27797
OpenTargetsiENSG00000179218
Orphaneti3318 Essential thrombocythemia
824 Myelofibrosis with myeloid metaplasia
PharmGKBiPA26046
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0674 Eukaryota
ENOG410XRR7 LUCA
GeneTreeiENSGT00430000030841
HOGENOMiHOG000192435
HOVERGENiHBG005407
InParanoidiP27797
KOiK08057
OMAiDTWIYSK
OrthoDBiEOG091G0AP1
PhylomeDBiP27797
TreeFamiTF338438

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-168316 Assembly of Viral Components at the Budding Site
R-HSA-3000480 Scavenging by Class A Receptors
R-HSA-3000484 Scavenging by Class F Receptors
R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-901042 Calnexin/calreticulin cycle
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC

Miscellaneous databases

ChiTaRSiCALR human
EvolutionaryTraceiP27797
GeneWikiiCalreticulin
GenomeRNAii811
PROiPR:P27797
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179218 Expressed in 236 organ(s), highest expression level in thyroid gland
CleanExiHS_CALR
ExpressionAtlasiP27797 baseline and differential
GenevisibleiP27797 HS

Family and domain databases

Gene3Di2.10.250.10, 1 hit
InterProiView protein in InterPro
IPR001580 Calret/calnex
IPR018124 Calret/calnex_CS
IPR009169 Calreticulin
IPR009033 Calreticulin/calnexin_P_dom_sf
IPR013320 ConA-like_dom_sf
PANTHERiPTHR11073 PTHR11073, 1 hit
PfamiView protein in Pfam
PF00262 Calreticulin, 2 hits
PIRSFiPIRSF002356 Calreticulin, 1 hit
PRINTSiPR00626 CALRETICULIN
SUPFAMiSSF49899 SSF49899, 1 hit
SSF63887 SSF63887, 1 hit
PROSITEiView protein in PROSITE
PS00803 CALRETICULIN_1, 1 hit
PS00804 CALRETICULIN_2, 1 hit
PS00805 CALRETICULIN_REPEAT, 3 hits
PS00014 ER_TARGET, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCALR_HUMAN
AccessioniPrimary (citable) accession number: P27797
Secondary accession number(s): Q6IAT4, Q9UDG2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: October 10, 2018
This is version 224 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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