Reviewed, UniProtKB/Swiss-Prot P15253 (CALR_RABIT)

Names and origin

Protein names

Recommended name:
Calreticulin

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

Gene names

Name:

CALR

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	418 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	Molecular calcium binding chaperone promoting folding, oligomeric assembly and quality control in the 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 By similarity. Ref.6
Subunit structure	Monomer. Component of an EIF2 complex at least composed of CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interacts with PDIA3/ERp57 and with NR3C1 By similarity.
Subcellular location	Endoplasmic reticulum lumen.
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. Ref.7 The interaction with glycans occurs through a binding site in the globular lectin domain By similarity. Ref.7 The zinc binding sites are localized to the N-domain. Ref.7 Associates with PDIA3 through the tip of the extended arm formed by the P-domain By similarity. Ref.7
Sequence similarities	Belongs to the calreticulin family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Domain	Repeat Signal
Ligand	Calcium Lectin Metal-binding Zinc
Molecular function	Chaperone
PTM	Acetylation Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	protein folding Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW sugar binding Inferred from electronic annotation. Source: UniProtKB-KW unfolded protein binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Ref.3 Ref.4
	Chain	18 – 418	401	Calreticulin		PRO_0000004176
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 – 418	110	C-domain
	Motif	415 – 418	4	Prevents secretion from ER
	Compositional bias	351 – 408	58	Asp/Glu/Lys-rich
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
Natural variations
	Natural variant	35	1	E → D
Experimental info
	Mutagenesis	170	1	H → A: Loss of activity. Ref.8
	Sequence conflict	90	1	P → T AA sequence Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P15253-1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: B6082B689DC763A6	FASTA	418	48,275
	10 20 30 40 50 60 MLLPVPLLLG LLGLAAAEPV VYFKEQFLDG DGWTERWIES KHKSDFGKFV LSSGKFYGDQ 70 80 90 100 110 120 EKDKGLQTSQ DARFYALSAR FEPFSNKGQP LVVQFTVKHE QNIDCGGGYV KLFPAGLDQK 130 140 150 160 170 180 DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN 190 200 210 220 230 240 TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDASKPEDWD 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 KTAEKQMKDK 370 380 390 400 410 QDEEQRLKEE EEEKKRKEEE EAEEDEEDKD DKEDEDEDEE DKDEEEEEAA AGQAKDEL

References

[1]	"Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum." Fliegel L., Burns K., Maclennan D.H., Reithmeier R.A.F., Michalak M. J. Biol. Chem. 264:21522-21528(1989) [PubMed: 2600080] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Slow-twitch skeletal muscle.
[2]	"Fast-twitch and slow-twitch skeletal muscles express the same isoform of calreticulin." Fliegel L., Michalak M. Biochem. Biophys. Res. Commun. 177:979-984(1991) [PubMed: 2059224] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fast-twitch skeletal muscle.
[3]	"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: 2241926] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-36.
[4]	"Calreticulin, and not calsequestrin, is the major calcium binding protein of smooth muscle sarcoplasmic reticulum and liver endoplasmic reticulum." Milner R.E., Baksh S., Shemanko C., Carpenter M.R., Smillie L., Vance J.E., Opas M., Michalak M. J. Biol. Chem. 266:7155-7165(1991) [PubMed: 2016321] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-46.
[5]	"Evidence for complex formation between rabbit lung flavin-containing monooxygenase and calreticulin." Guan S., Falick A.M., Williams D.E., Cashman J.R. Biochemistry 30:9892-9900(1991) [PubMed: 1911780] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE. Tissue: Lung.
[6]	"Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins." Saito Y., Ihara Y., Leach M.R., Cohen-Doyle M.F., Williams D.B. EMBO J. 18:6718-6729(1999) [PubMed: 10581245] [Abstract] Cited for: FUNCTION.
[7]	"Identification of the Zn2+ binding region in calreticulin." Baksh S., Spamer C., Heilmann C., Michalak M. FEBS Lett. 376:53-57(1995) [PubMed: 8521965] [Abstract] Cited for: ZINC-BINDING DOMAIN.
[8]	"Identification of an N-domain histidine essential for chaperone function in calreticulin." Guo L., Groenendyk J., Papp S., Dabrowska M., Knoblach B., Kay C., Parker J.M., Opas M., Michalak M. J. Biol. Chem. 278:50645-50653(2003) [PubMed: 14522955] [Abstract] Cited for: MUTAGENESIS OF HIS-170.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J05138 mRNA. Translation: AAA31188.1.
PIR	A34154. C33208. D33208. S13046.
RefSeq	NP_001075704.1.
UniGene	Ocu.1840
3D structure databases
SMR	P15253. Positions 206-305.
ModBase	Search...
Genome annotation databases
GeneID	100009050.
Organism-specific databases
CTD	100009050.
Phylogenomic databases
eggNOG	maNOG07829.
HOVERGEN	HBG005407.
Family and domain databases
InterPro	IPR001580. Calret/calnex. IPR018124. Calret/calnex_CS. IPR009169. Calreticulin. IPR009033. Calreticulin/calnexin_P. IPR008985. ConA-like_lec_gl. IPR013320. ConA-like_subgrp. [Graphical view]
Gene3D	G3DSA:2.10.250.10. Calreticulin/calnexin_P. 1 hit. G3DSA:2.60.120.200. ConA_like_subgrp. 1 hit.
PANTHER	PTHR11073. Calret/calnex. 1 hit. PTHR11073:SF2. Calreticulin. 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...

Entry information

Entry name

CALR_RABIT

Accession

Primary (citable) accession number: P15253

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	March 2, 2010
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)