P14211 (CALR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calreticulin

Alternative name(s):
CRP55
Calregulin
Endoplasmic reticulum resident protein 60
Short name=ERp60
HACBP

Gene names

Name:

Calr

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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. Ref.9 Ref.10
Subunit structure	Monomer. Interacts with GABARAP, NR3C1, PDIA3/ERp57 and TRIM21 By similarity. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Ref.8
Subcellular location	Endoplasmic reticulum lumen. Cytoplasmic granule. Sarcoplasmic reticulum lumen By similarity. Note: Associated with the lytic granules in the cytolytic T-lymphocytes. Ref.7
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 By similarity.
Sequence similarities	Belongs to the calreticulin family.

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 electronic annotation. Source: Compara cell cycle arrest Inferred from electronic annotation. Source: Compara cellular response to lithium ion Inferred from electronic annotation. Source: Compara cellular response to organic substance Inferred from electronic annotation. Source: Compara cellular senescence Inferred from mutant phenotype PubMed 14726956. Source: BHF-UCL cortical actin cytoskeleton organization Inferred from direct assay PubMed 15136153. Source: MGI 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 electronic annotation. Source: Compara peptide antigen assembly with MHC class I protein complex Inferred from mutant phenotype PubMed 11825569. Source: BHF-UCL positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of cell cycle Inferred from mutant phenotype PubMed 14726956. Source: BHF-UCL positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from mutant phenotype PubMed 15998798. Source: UniProtKB positive regulation of phagocytosis Inferred from mutant phenotype PubMed 17187072. Source: BHF-UCL protein export from nucleus Inferred from electronic annotation. Source: Compara protein folding Inferred from electronic annotation. Source: InterPro protein localization to nucleus Inferred from mutant phenotype PubMed 15998798. Source: UniProtKB protein stabilization Inferred from direct assay Ref.10. Source: UniProtKB regulation of meiosis Inferred from direct assay PubMed 15136153. Source: MGI response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to testosterone stimulus Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara MHC class I peptide loading complex Inferred from mutant phenotype PubMed 11825569. Source: BHF-UCL acrosomal vesicle Inferred from electronic annotation. Source: Compara cytosol Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from direct assay PubMed 15136153. Source: MGI extracellular matrix Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 15136153. Source: MGI nucleus Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara phagocytic vesicle Traceable author statement. Source: Reactome polysome Inferred from direct assay PubMed 14726956. Source: BHF-UCL sarcoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from direct assay Ref.10. Source: UniProtKB carbohydrate binding Inferred from direct assay Ref.9. Source: UniProtKB hormone binding Inferred from electronic annotation. Source: Compara iron ion binding Inferred from electronic annotation. Source: Compara mRNA binding Inferred from direct assay PubMed 14726956. Source: BHF-UCL peptide binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.1 Ref.5

Chain

18 – 416

399

Calreticulin

PRO_0000004174

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

Metal binding

62

1

Calcium; via carbonyl oxygen

Metal binding

64

1

Calcium; via carbonyl oxygen

Metal binding

328

1

Calcium

Binding site

109

1

Carbohydrate

Binding site

111

1

Carbohydrate

Binding site

128

1

Carbohydrate

Binding site

135

1

Carbohydrate

Binding site

317

1

Carbohydrate

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

Ref.9 Ref.10

Experimental info

Sequence conflict

272

1

K → R in BAE35687. Ref.3

Sequence conflict

407

1

E → Q in BAE35687. Ref.3

Secondary structure

1

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416

Helix Strand Turn

Details...

Beta strand

21 – 25

5

Helix

30 – 35

6

Beta strand

37 – 39

3

Beta strand

42 – 44

3

Beta strand

49 – 52

4

Turn

60 – 63

4

Beta strand

65 – 68

4

Beta strand

70 – 84

15

Beta strand

91 – 98

8

Beta strand

104 – 107

4

Beta strand

110 – 113

4

Helix

119 – 121

3

Beta strand

129 – 137

9

Turn

138 – 140

3

Beta strand

141 – 150

10

Beta strand

153 – 156

4

Beta strand

166 – 176

11

Beta strand

180 – 186

7

Beta strand

189 – 195

7

Helix

196 – 199

4

Beta strand

206 – 209

4

Beta strand

293 – 295

3

Turn

303 – 306

4

Beta strand

311 – 322

12

Beta strand

326 – 334

9

Helix

336 – 345

10

Helix

347 – 360

14

Sequences

	Sequence		Length	Mass (Da)
	P14211 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 24C03B00913408D8	FASTA	416	47,995
	10 20 30 40 50 60 MLLSVPLLLG LLGLAAADPA IYFKEQFLDG DAWTNRWVES KHKSDFGKFV LSSGKFYGDL 70 80 90 100 110 120 EKDKGLQTSQ DARFYALSAK FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPSGLDQK 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 EAEDKEDDDD RDEDEDEEDE KEEDEEESPG QAKDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Multiple zones in the sequence of calreticulin (CRP55, calregulin, HACBP), a major calcium binding ER/SR protein." Smith M.J., Koch G.L.E. EMBO J. 8:3581-3586(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-48 AND 129-161. Strain: BALB/c. Tissue: Liver.
[2]	"Determination of the sequence of an expressible cDNA clone encoding ERp60/calregulin by the use of a novel nested set method." Mazzarella R.A., Gold P., Cunningham M., Green M. Gene 120:217-225(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Brain and 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]. Strain: FVB/N-3. Tissue: Mammary gland.
[5]	"Separation and sequencing of familiar and novel murine proteins using preparative two-dimensional gel electrophoresis." Merrick B.A., Patterson R.M., Wichter L.L., He C., Selkirk J.K. Electrophoresis 15:735-745(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-38. Tissue: Fibroblast.
[6]	Lubec G., Kang S.U., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 25-36; 56-64; 74-151; 154-159; 163-222; 225-272; 323-351; 341-357 AND 392-413, MASS SPECTROMETRY. Strain: C57BL/6 and OF1. Tissue: Brain and Hippocampus.
[7]	"The calcium-binding protein calreticulin is a major constituent of lytic granules in cytolytic T lymphocytes." Dupuis M., Schaerer E., Krause K.-H., Tschopp J. J. Exp. Med. 177:1-7(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-binding protein beta in old liver." Timchenko L.T., Salisbury E., Wang G.-L., Nguyen H., Albrecht J.H., Hershey J.W., Timchenko N.A. J. Biol. Chem. 281:32806-32819(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN AN EIF2 COMPLEX WITH EIF2S1; EIF2S2; CELF1; CALR3; HSPA5 AND HSP90B1.
[9]	"Structural basis of carbohydrate recognition by calreticulin." Kozlov G., Pocanschi C.L., Rosenauer A., Bastos-Aristizabal S., Gorelik A., Williams D.B., Gehring K. J. Biol. Chem. 285:38612-38620(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 18-368 IN COMPLEX WITH CALCIUM AND TETRASACCHARIDE, FUNCTION, MASS SPECTROMETRY, DISULFIDE BOND.
[10]	"Structural and functional relationships between the lectin and arm domains of calreticulin." Pocanschi C.L., Kozlov G., Brockmeier U., Brockmeier A., Williams D.B., Gehring K. J. Biol. Chem. 286:27266-27277(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.57 ANGSTROMS) OF 18-368 IN COMPLEX WITH CALCIUM IONS, FUNCTION, DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X14926 mRNA. Translation: CAA33053.1.
M92988 mRNA. Translation: AAA37569.1.
AK075605 mRNA. Translation: BAC35852.1.
AK160197 mRNA. Translation: BAE35687.1.
BC003453 mRNA. Translation: AAH03453.1.

IPI

IPI00123639.

PIR

S06763.

RefSeq

NP_031617.1. NM_007591.3.

UniGene

Mm.1971.
Mm.467043.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3O0V	X-ray	2.30	A	18-368	[»]
3O0W	X-ray	1.95	A	18-368	[»]
3O0X	X-ray	2.01	A/B	18-368	[»]
3RG0	X-ray	2.57	A	18-368	[»]

ProteinModelPortal

P14211.

SMR

P14211. Positions 18-367.

ModBase

Search...

Protein-protein interaction databases

IntAct

P14211. 7 interactions.

PTM databases

PhosphoSite

P14211.

2D gel databases

COMPLUYEAST-2DPAGE

P14211.

REPRODUCTION-2DPAGE

IPI00123639.
P14211.

SWISS-2DPAGE

P14211.

Proteomic databases

PaxDb

P14211.

PRIDE

P14211.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000003912; ENSMUSP00000003912; ENSMUSG00000003814.

GeneID

12317.

KEGG

mmu:12317.

Organism-specific databases

CTD

811.

MGI

MGI:88252. Calr.

Phylogenomic databases

eggNOG

NOG305105.

GeneTree

ENSGT00430000030841.

HOGENOM

HOG000192435.

HOVERGEN

HBG005407.

InParanoid

P14211.

KO

K08057.

OMA

EWEAPTI.

OrthoDB

EOG41JZCD.

Enzyme and pathway databases

Reactome

REACT_102124. Immune System.

Gene expression databases

ArrayExpress

P14211.

Bgee

P14211.

CleanEx

MM_CALR.

Genevestigator

P14211.

GermOnline

ENSMUSG00000003814. Mus musculus.

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

ChiTaRS

CALR. mouse.

EvolutionaryTrace

Q3TVD2.

NextBio

280884.

SOURCE

Search...

Entry information

Entry name

CALR_MOUSE

Accession

Primary (citable) accession number: P14211
Secondary accession number(s): Q3TVD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	April 3, 2013
This is version 144 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program