PROSITE documentation PDOC00636
Calreticulin family signatures


Calreticulin [1] (also known as calregulin, CRP55 or HACBP) is a high-capacity calcium-binding protein which is present in most tissues and located at the periphery of the endoplasmic (ER) and the sarcoplamic reticulum (SR) membranes. It probably plays a role in the storage of calcium in the lumen of the ER and SR and it may well have other important functions. Structurally, calreticulin is a protein of about 400 amino acid residues consisting of three domains:

 a) An N-terminal, probably globular, domain  of about 180 amino acid residues
 b) A central domain  of about  70 residues (P-domain)  which  contains  three
    repeats of an acidic 17 amino acid motif. This region binds calcium with a
    low-capacity, but a high-affinity;
 c) A C-terminal domain rich in acidic residues and in lysine (C-domain). This
    region binds calcium with a high-capacity but a low-affinity.

Calreticulin is evolutionary related to the following proteins:

  • Onchocerca volvulus antigen RAL-1. RAL-1 is highly similar to calreticulin, but possesses a C-terminal domain rich in lysine and arginine and lacks acidic residues and is therefore not expected to bind calcium in that region.
  • Calnexin [2]. A calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins.
  • Calmegin [3] (or calnexin-T), a testis-specific calcium-binding protein highly similar to calnexin.

We developed three signature patterns for this family of proteins. The first two patterns are based on conserved regions in the N-domain; the third pattern corresponds to positions 4 to 16 of the repeated motif in the P-domain.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

CALRETICULIN_1, PS00803; Calreticulin family signature 1  (PATTERN)

CALRETICULIN_2, PS00804; Calreticulin family signature 2  (PATTERN)

CALRETICULIN_REPEAT, PS00805; Calreticulin family repeated motif signature  (PATTERN)


1AuthorsMichalak M. Milner R.E. Burns K. Opas M.
SourceBiochem. J. 285:681-692(1992).
PubMed ID1497605

2AuthorsBergeron J.J.M. Brenner M.B. Thomas D.Y. Williams D.B.
TitleCalnexin: a membrane-bound chaperone of the endoplasmic reticulum.
SourceTrends Biochem. Sci. 19:124-128(1994).
PubMed ID8203019

3AuthorsWatanabe D. Yamada K. Nishina Y. Tajima Y. Koshimizu U. Nagata A. Nishimune Y.
TitleMolecular cloning of a novel Ca(2+)-binding protein (calmegin) specifically expressed during male meiotic germ cell development.
SourceJ. Biol. Chem. 269:7744-7749(1994).
PubMed ID8126001

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