Seroatlas · Human Serome Atlas

CALR

Calreticulin

Also known as: CALR_HUMAN, cC1qR, CRT, FLJ26680, RO, SSA

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P27797
Gene
CALR
Ensembl
ENSG00000179218
Chromosome
19
Canonical length
417 aa
Protein class
Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters
Subcellular location
Endoplasmic reticulum
Secretome location
Intracellular and membrane

OverviewNCBI Gene

Calreticulin is a highly conserved chaperone protein which resides primarily in the endoplasmic reticulum, and is involved in a variety of cellular processes, among them, cell adhesion. Additionally, it functions in protein folding quality control and calcium homeostasis. Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription regulation. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin. Recurrent mutations in calreticulin have been linked to various neoplasms, including the myeloproliferative type.[provided by RefSeq, May 2020]

Canonical amino-acid sequenceUniProt

417 residues, UniProt reviewed canonical sequence.

>P27797|CALR
     1  MLLSVPLLLG LLGLAVAEPA VYFKEQFLDG DGWTSRWIES KHKSDFGKFV LSSGKFYGDE
    61  EKDKGLQTSQ DARFYALSAS FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPNSLDQT
   121  DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN
   181  TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDASKPEDWD ERAKIDDPTD SKPEDWDKPE
   241  HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS
   301  PDPSIYAYDN FGVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KAAEKQMKDK
   361  QDEEQRLKEE EEDKKRKEEE EAEDKEDDED KDEDEEDEED KEEDEEEDVP GQAKDEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CALR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.34
Highest tissue expression
717 nTPM

Expression across tissuesHPA

Tissue

  • liver: 717 nTPM
  • thyroid gland: 658 nTPM
  • epididymis: 612 nTPM
  • bone marrow: 523 nTPM
  • choroid plexus: 476 nTPM
  • placenta: 379 nTPM

Single-cell type

  • extravillous trophoblasts: 2,367 nCPM
  • syncytiotrophoblasts: 1,174 nCPM
  • esophageal apical cells: 1,119 nCPM
  • plasma cells: 910 nCPM
  • epididymal principal cells: 908 nCPM
  • migrating cytotrophoblasts: 877 nCPM

Immune cell

  • plasmacytoid DC: 216 nTPM
  • gdT-cell: 173 nTPM
  • intermediate monocyte: 148 nTPM
  • naive CD8 T-cell: 135 nTPM
  • memory CD8 T-cell: 130 nTPM
  • non-classical monocyte: 123 nTPM

Brain region

  • choroid plexus: 493 nTPM
  • white matter: 387 nTPM
  • thalamus: 387 nTPM
  • medulla oblongata: 363 nTPM
  • pons: 319 nTPM
  • hypothalamus: 314 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CALR.

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 95 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Disease | ImmuneIEDB

Conditions an epitope on CALR was assayed in.

Disease | AutoantibodyPubMed

Conditions in which antibodies against CALR are reported. Each links to that disease's full target list.

ReferencesPubMed · IEDB

Publications for CALR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

29 publications

Show 20 more of 29 total

Reference: B cellIEDB

6 publications

Show 1 more

Reference: T cellIEDB

2 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.38
gnomAD pLI
0.89
gnomAD missense Z
0.29
DepMap mean gene effect
-0.14
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CALR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CALR as an antibody target. Whether an autoantibody or antibody against CALR could matter depends on whether native CALR is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CALR is annotated at the cell surface, where native CALR is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

  • Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin.

Canonical record: https://seroatlas.com/gene/CALR. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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