P18418 (CALR_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calreticulin

Alternative name(s):
CALBP
CRP55
Calcium-binding protein 3
Short name=CABP3
Calregulin
Endoplasmic reticulum resident protein 60
Short name=ERp60
HACBP

Gene names

Name:

Calr

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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.
Subunit structure	Monomer. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interacts with GABARAP, NR3C1 and TRIM21 By similarity. Interacts with PDIA3/ERp57. Ref.11
Subcellular location	Endoplasmic reticulum lumen. Sarcoplasmic reticulum lumen By similarity Ref.10.
Tissue specificity	Predentin and odontoblast. Ref.10
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 By similarity. The interaction with glycans occurs through a binding site in the globular lectin domain By similarity. The zinc binding sites are localized to the N-domain By similarity. Associates with PDIA3 through the tip of the extended arm formed by the P-domain.
Sequence similarities	Belongs to the calreticulin family.
Caution	Was originally (Ref.9) thought to be D-beta-hydroxybutyrate dehydrogenase.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Sarcoplasmic reticulum
Domain	Repeat Signal
Ligand	Calcium Lectin Metal-binding Zinc
Molecular function	Chaperone
PTM	Acetylation Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle cell differentiation Inferred from expression pattern PubMed 9011638. Source: RGD cell cycle arrest Inferred from electronic annotation. Source: Compara cellular response to lithium ion Inferred from expression pattern PubMed 16236328. Source: RGD cellular response to organic substance Inferred from expression pattern PubMed 10833321. Source: RGD cellular senescence Inferred from electronic annotation. Source: Compara chaperone-mediated protein folding Inferred from mutant phenotype PubMed 12401114. Source: RGD cortical actin cytoskeleton organization Inferred from electronic annotation. Source: Compara negative regulation of intracellular steroid hormone receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara negative regulation of retinoic acid receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of translation Inferred from direct assay PubMed 14726956. Source: BHF-UCL peptide antigen assembly with MHC class I protein complex Inferred from electronic annotation. Source: Compara positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of cell cycle Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of phagocytosis Inferred from electronic annotation. Source: Compara protein export from nucleus Inferred from electronic annotation. Source: Compara protein localization to nucleus Inferred from electronic annotation. Source: Compara protein stabilization Inferred from sequence or structural similarity. Source: UniProtKB regulation of meiosis Inferred from electronic annotation. Source: Compara response to drug Inferred from expression pattern PubMed 11032977. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 16339744. Source: RGD response to testosterone stimulus Inferred from expression pattern PubMed 9751517. Source: RGD spermatogenesis Inferred from expression pattern Ref.2. Source: RGD
Cellular_component	Golgi apparatus Inferred from direct assay Ref.2. Source: RGD MHC class I peptide loading complex Inferred from electronic annotation. Source: Compara acrosomal vesicle Inferred from direct assay Ref.2. Source: RGD cell surface Inferred from direct assay PubMed 11891802. Source: RGD cytosol Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular matrix Inferred from direct assay Ref.10. Source: RGD extracellular space Inferred from direct assay Ref.10. Source: RGD nucleus Inferred from direct assay PubMed 12603316. Source: RGD perinuclear region of cytoplasm Inferred from direct assay PubMed 8600158. Source: RGD polysome Inferred from electronic annotation. Source: Compara protein complex Inferred from direct assay PubMed 12401114. Source: RGD sarcoplasmic reticulum Inferred from direct assay PubMed 8600158. Source: RGD sarcoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from direct assay PubMed 8500729. Source: RGD carbohydrate binding Inferred from electronic annotation. Source: Compara hormone binding Inferred from physical interaction PubMed 12603316. Source: RGD iron ion binding Inferred from direct assay PubMed 8500729. Source: RGD mRNA binding Inferred from direct assay PubMed 14726956. Source: BHF-UCL peptide binding Inferred from direct assay PubMed 10833321. Source: RGD unfolded protein binding Inferred from mutant phenotype PubMed 12401114. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.5 Ref.6 Ref.7

Chain

18 – 416

399

Calreticulin

PRO_0000004177

Regions

Repeat

191 – 202

12

1-1

Repeat

210 – 221

12

1-2

Repeat

227 – 238

12

1-3

Repeat

244 – 255

12

1-4

Repeat

259 – 269

11

2-1

Repeat

273 – 283

11

2-2

Repeat

287 – 297

11

2-3

Region

18 – 197

180

N-domain

Region

191 – 255

65

4 X approximate repeats

Region

198 – 308

111

P-domain

Region

259 – 297

39

3 X approximate repeats

Region

309 – 416

108

C-domain

Motif

413 – 416

4

Prevents secretion from ER

Compositional bias

351 – 407

57

Asp/Glu/Lys-rich

Sites

Metal binding

26

1

Calcium; via carbonyl oxygen By similarity

Metal binding

62

1

Calcium; via carbonyl oxygen By similarity

Metal binding

64

1

Calcium; via carbonyl oxygen By similarity

Metal binding

328

1

Calcium By similarity

Binding site

109

1

Carbohydrate By similarity

Binding site

111

1

Carbohydrate By similarity

Binding site

128

1

Carbohydrate By similarity

Binding site

135

1

Carbohydrate By similarity

Binding site

317

1

Carbohydrate By similarity

Amino acid modifications

Modified residue

48

1

N6-acetyllysine By similarity

Modified residue

159

1

N6-acetyllysine By similarity

Modified residue

209

1

N6-acetyllysine By similarity

Disulfide bond

105 ↔ 137

By similarity

Experimental info

Sequence conflict

269

1

P → R in CAA31987. Ref.9

Sequence conflict

359 – 361

3

DKQ → AAG in CAA31987. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

416

Helix Strand Turn

Details...

Turn

220 – 222

3

Beta strand

223 – 225

3

Turn

234 – 236

3

Beta strand

240 – 243

4

Helix

255 – 258

4

Beta strand

265 – 267

3

Beta strand

301 – 303

3

Sequences

	Sequence		Length	Mass (Da)
	P18418 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: 2E6713CED31A2970	FASTA	416	47,995
	10 20 30 40 50 60 MLLSVPLLLG LLGLAAADPA IYFKEQFLDG DAWTNRWVES KHKSDFGKFV LSSGKFYGDQ 70 80 90 100 110 120 EKDKGLQTSQ DARFYALSAR FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPGGLDQK 130 140 150 160 170 180 DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN 190 200 210 220 230 240 TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDAAKPEDWD ERAKIDDPTD SKPEDWDKPE 250 260 270 280 290 300 HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS 310 320 330 340 350 360 PDANIYAYDS FAVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KAAEKQMKDK 370 380 390 400 410 QDEEQRLKEE EEDKKRKEEE EAEDKEDEDD RDEDEDEEDE KEEDEEDATG QAKDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural homology between the rat calreticulin gene product and the Onchocerca volvulus antigen Ral-1." Murthy K.K., Banville D., Srikant C.B., Carrier F., Bell A., Holmes C., Patel Y.C. Nucleic Acids Res. 18:4933-4933(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Brain cortex.
[2]	"An endoplasmic reticulum protein, calreticulin, is transported into the acrosome of rat sperm." Nakamura M., Moriya M., Baba T., Michikawa Y., Yamanobe T., Arai K., Okinaga S., Kobayashi T. Exp. Cell Res. 205:101-110(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley.
[3]	"Retention and retrieval: both mechanisms cooperate to maintain calreticulin in the endoplasmic reticulum." Soennichsen B., Fuellekrug J., van Nguyen P., Diekmann W., Robinson D.G., Mieskes G. J. Cell Sci. 107:2705-2717(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Liver.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[5]	"Calreticulin is present in the acrosome of spermatids of rat testis." Nakamura M., Michikawa Y., Baba T., Okinaga S., Arai K. Biochem. Biophys. Res. Commun. 186:668-673(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32. Strain: Sprague-Dawley. Tissue: Testis.
[6]	"Identification of protein disulfide isomerase and calreticulin as autoimmune antigens in LEC strain of rats." Yokoi T., Nagayama S., Kajiwara R., Kawaguchi Y., Horiuchi R., Kamataki T. Biochim. Biophys. Acta 1158:339-344(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32. Strain: LEC. Tissue: Liver.
[7]	"Calreticulin is a candidate for a calsequestrin-like function in Ca2(+)-storage compartments (calciosomes) of liver and brain." Treves S., de Mattei M., Lanfredi M., Villa A., Green N.M., Maclennan D.H., Meldolesi J., Pozzan T. Biochem. J. 271:473-480(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-29.
[8]	Lubec G., Afjehi-Sadat L., Diao W. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 25-36; 88-98 AND 163-185, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus and Spinal cord.
[9]	Lone Y.-C., Bailly A., Latruffe N. Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 269-361. Strain: Sprague-Dawley.
[10]	"Calreticulin -- an endoplasmic reticulum protein with calcium-binding activity is also found in the extracellular matrix." Somogyi E., Petersson U., Hultenby K., Wendel M. Matrix Biol. 22:179-191(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[11]	"TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain." Frickel E.M., Riek R., Jelesarov I., Helenius A., Wuethrich K., Ellgaard L. Proc. Natl. Acad. Sci. U.S.A. 99:1954-1959(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDIA3.
[12]	"NMR structure of the calreticulin P-domain." Ellgaard L., Riek R., Herrmann T., Guntert P., Braun D., Helenius A., Wuthrich K. Proc. Natl. Acad. Sci. U.S.A. 98:3133-3138(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 206-305.
[13]	"NMR structures of 36 and 73-residue fragments of the calreticulin P-domain." Ellgaard L., Bettendorff P., Braun D., Herrmann T., Fiorito F., Jelesarov I., Guntert P., Helenius A., Wuthrich K. J. Mol. Biol. 322:773-784(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 206-278.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X53363 mRNA. Translation: CAA37446.1.
D78308 mRNA. Translation: BAA11345.1.
X79327 mRNA. Translation: CAA55890.1.
BC062395 mRNA. Translation: AAH62395.1.
X13702 mRNA. Translation: CAA31987.1.

IPI

IPI00191728.

PIR

JH0819.

RefSeq

NP_071794.1. NM_022399.2.

UniGene

Rn.974.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HHN	NMR	-	A	206-305	[»]
1K91	NMR	-	A	238-273	[»]
1K9C	NMR	-	A	206-278	[»]

ProteinModelPortal

P18418.

SMR

P18418. Positions 206-305.

ModBase

Search...

Protein-protein interaction databases

IntAct

P18418. 2 interactions.

2D gel databases

World-2DPAGE

0004:P18418.

Proteomic databases

PaxDb

P18418.

PRIDE

P18418.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000004091; ENSRNOP00000004091; ENSRNOG00000003029.

GeneID

64202.

KEGG

rno:64202.

Organism-specific databases

CTD

811.

RGD

620288. Calr.

Phylogenomic databases

eggNOG

NOG305105.

GeneTree

ENSGT00430000030841.

HOGENOM

HOG000192435.

HOVERGEN

HBG005407.

InParanoid

P18418.

KO

K08057.

OMA

EWEAPTI.

OrthoDB

EOG41JZCD.

Gene expression databases

Genevestigator

P18418.

GermOnline

ENSRNOG00000003029. Rattus norvegicus.

Family and domain databases

Gene3D

2.60.120.200. 2 hits.

InterPro

IPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009169. Calreticulin.
IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
[Graphical view]

PANTHER

PTHR11073. PTHR11073. 1 hit.

Pfam

PF00262. Calreticulin. 1 hit.
[Graphical view]

PIRSF

PIRSF002356. Calreticulin. 1 hit.

PRINTS

PR00626. CALRETICULIN.

SUPFAM

SSF49899. ConA_like_lec_gl. 2 hits.

PROSITE

PS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00805. CALRETICULIN_REPEAT. 3 hits.
PS00014. ER_TARGET. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P18418.

NextBio

612898.

Entry information

Entry name

CALR_RAT

Accession

Primary (citable) accession number: P18418
Secondary accession number(s): P10452

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	April 3, 2013
This is version 135 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program