Reviewed, UniProtKB/Swiss-Prot P27797 (CALR_HUMAN)

Names and origin

Protein names

Recommended name:
    Calreticulin
Alternative name(s):
    CRP55
    Calregulin
    HACBP
    ERp60
    grp60

Gene names

Name:	CALR
Synonyms:	CRTC

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	417 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. Ref.15 Ref.17
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. Cytoplasm › cytosol. Secreted › extracellular space › extracellular matrix. Cell surface. Note: Also found in cell surface (T cells), cytosol and extracellular matrix. Associated with the lytic granules in the cytolytic T-lymphocytes. Ref.17 Ref.13 Ref.16
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. The interaction with glycans occurs through a binding site in the globular lectin domain. The zinc binding sites are localized to the N-domain. 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.1) thought to be the 52 kDa Ro autoantigen.
Mass spectrometry	Molecular mass is 46879 Da from positions 18 - 417. Determined by MALDI. Ref.17

Ontologies

Keywords
Cellular component	Cytoplasm Endoplasmic reticulum Extracellular matrix Secreted
Domain	Repeat Signal
Ligand	Calcium Lectin Metal-binding Zinc
Molecular function	Chaperone
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell cycle arrest Inferred from genetic interaction. Source: UniProtKB glucocorticoid receptor signaling pathway Traceable author statement. Source: UniProtKB negative regulation of neuron differentiation Inferred from direct assay. Source: UniProtKB negative regulation of retinoic acid receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of steroid hormone receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB negative regulation of translation Traceable author statement. Source: UniProtKB peptide antigen assembly with MHC class I protein complex Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of DNA replication Inferred from genetic interaction. Source: UniProtKB positive regulation of cell cycle Inferred from genetic interaction. Source: UniProtKB positive regulation of cell proliferation Inferred from genetic interaction. Source: UniProtKB positive regulation of phagocytosis Inferred from sequence or structural similarity. Source: UniProtKB protein export from nucleus Ref.17 Inferred from direct assay. Source: UniProtKB protein maturation by protein folding Traceable author statement. Source: UniProtKB protein stabilization Traceable author statement. Source: UniProtKB regulation of apoptosis Traceable author statement. Source: UniProtKB senescence Inferred from genetic interaction. Source: UniProtKB sequestering of calcium ion Traceable author statement. Source: UniProtKB
Cellular component	MHC class I peptide loading complex Inferred from sequence or structural similarity. Source: UniProtKB cytosol Ref.17 Inferred from direct assay. Source: UniProtKB endoplasmic reticulum lumen Ref.17 Inferred from direct assay. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Ref.8 Inferred from direct assay. Source: UniProtKB polysome Inferred from sequence or structural similarity. Source: UniProtKB proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Ref.17 Non-traceable author statement. Source: UniProtKB androgen receptor binding Inferred from direct assay. Source: UniProtKB calcium ion binding Ref.17 Traceable author statement. Source: UniProtKB chaperone binding Traceable author statement. Source: UniProtKB complement component C1q binding Traceable author statement. Source: UniProtKB integrin binding Ref.8 Inferred from physical interaction. Source: UniProtKB mRNA binding Inferred from direct assay. Source: UniProtKB sugar binding Inferred from electronic annotation. Source: UniProtKB-KW transcription repressor activity Inferred from direct assay. Source: UniProtKB unfolded protein binding Traceable author statement. Source: UniProtKB zinc ion binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD40	P25942	1	EBI-1049597,EBI-525714
ELF3	P78545	1	EBI-1049597,EBI-1057285
EPB41	P11171	1	EBI-1049597,EBI-1050906
TAP1	Q03518	1	EBI-1049597,EBI-747259

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Ref.13 Ref.7 Ref.8 Ref.9 Ref.10 Ref.14
	Chain	18 – 417	400	Calreticulin		PRO_0000004173
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 – 417	109	C-domain
	Motif	414 – 417	4	Prevents secretion from ER
	Compositional bias	351 – 408	58	Asp/Glu/Lys-rich
Amino acid modifications
	Glycosylation	344	1	N-linked (GlcNAc...)
	Disulfide bond	105 ↔ 137		Ref.18
Experimental info
	Sequence conflict	35	1	Missing Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P27797-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: BC37C3C0F1054FB2	FASTA	417	48,142
	10 20 30 40 50 60 MLLSVPLLLG LLGLAVAEPA VYFKEQFLDG DGWTSRWIES KHKSDFGKFV LSSGKFYGDE 70 80 90 100 110 120 EKDKGLQTSQ DARFYALSAS FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPNSLDQT 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 PDPSIYAYDN FGVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KAAEKQMKDK 370 380 390 400 410 QDEEQRLKEE EEDKKRKEEE EAEDKEDDED KDEDEEDEED KEEDEEEDVP GQAKDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen." McCauliffe D.P., Lux F.A., Lieu T.S., Sanz I., Hanke J., Newkirk M.M., Bachinski L.L., Itoh Y., Siciliano M.J., Reichlin M., Sontheimer R.D., Capra J.D. J. Clin. Invest. 85:1379-1391(1990) [PubMed: 2332496] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Characterization of the autoantigen calreticulin." Rokeach L.A., Haselby J.A., Meilof J.F., Smeenk R.J., Unnasch T.R., Greene B.M., Hoch S.O. J. Immunol. 147:3031-3039(1991) [PubMed: 1919005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters." McCauliffe D.P., Yang Y.S., Wilson J., Sontheimer R.D., Capra J.D. J. Biol. Chem. 267:2557-2562(1992) [PubMed: 1733953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Liu J., Peng X., Yuan J., Qiang B. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye, Pancreas and Skin.
[7]	"Molecular characterization of human Ro/SS-A antigen. Amino terminal sequence of the protein moiety of human Ro/SS-A antigen and immunological activity of a corresponding synthetic peptide." Lieu T.-S., Newkirk M.M., Capra J.D., Sontheimer R.D. J. Clin. Invest. 82:96-101(1988) [PubMed: 3260607] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-41.
[8]	"In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits." Rojiani M.V., Finlay B.B., Gray V., Dedhar S. Biochemistry 30:9859-9866(1991) [PubMed: 1911778] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-36.
[9]	"Sequence similarity of calreticulin with a Ca2(+)-binding protein that co-purifies with an Ins(1,4,5)P3-sensitive Ca2+ store in HL-60 cells." Krause K.-H., Simmerman H.K.B., Jones L.R., Campbell K.P. Biochem. J. 270:545-548(1990) [PubMed: 2400400] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32.
[10]	"Human liver protein map: a reference database established by microsequencing and gel comparison." Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J. Electrophoresis 13:992-1001(1992) [PubMed: 1286669] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-28. Tissue: Liver.
[11]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 25-36; 74-111 AND 208-222, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[12]	"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes." Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J. Electrophoresis 13:960-969(1992) [PubMed: 1286667] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 25-34; 56-62; 208-221 AND 273-278. Tissue: Keratinocyte.
[13]	"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: 8418194] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-27, SUBCELLULAR LOCATION.
[14]	"A two-dimensional gel database of human colon carcinoma proteins." Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J. Electrophoresis 18:605-613(1997) [PubMed: 9150948] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-26. Tissue: Colon carcinoma.
[15]	"Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase." Nauseef W.M., McCormick S.J., Clark R.A. J. Biol. Chem. 270:4741-4747(1995) [PubMed: 7876246] [Abstract] Cited for: FUNCTION.
[16]	"Calreticulin is expressed on the cell surface of activated human peripheral blood T lymphocytes in association with major histocompatibility complex class I molecules." Arosa F.A., de Jesus O., Porto G., Carmo A.M., de Sousa M. J. Biol. Chem. 274:16917-16922(1999) [PubMed: 10358038] [Abstract] Cited for: SUBCELLULAR LOCATION.
[17]	"Calreticulin is a receptor for nuclear export." Holaska J.M., Black B.E., Love D.C., Hanover J.A., Leszyk J., Paschal B.M. J. Cell Biol. 152:127-140(2001) [PubMed: 11149926] [Abstract] Cited for: FUNCTION, INTERACTION WITH NR3C1, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
[18]	"Human placental calreticulin characterization of domain structure and post-translational modifications." Hoejrup P., Roepstorff P., Houen G. Eur. J. Biochem. 268:2558-2565(2001) [PubMed: 11322874] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, DISULFIDE BOND. Tissue: Placenta.
[19]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[20]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-344, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

Wikipedia

Calreticulin entry

Functional Glycomics Gateway - Glycan Binding

Calreticulin

Cross-references

Sequence databases

EMBLGenBankDDBJ

M32294 mRNA. Translation: AAA36582.1.
M84739 mRNA. Translation: AAA51916.1.
AY047586 mRNA. Translation: AAL13126.1.
AD000092 Genomic DNA. Translation: AAB51176.1.
BC002500 mRNA. Translation: AAH02500.1.
BC007911 mRNA. Translation: AAH07911.1.
BC020493 mRNA. Translation: AAH20493.1.

IPI

IPI00020599.

PIR

A37047. A42330.

RefSeq

NP_004334.1.

UniGene

Hs.515162

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CLR	X-ray	2.00	C/F	1-10	[»]
3DOW	X-ray	2.30	B	195-205	[»]

SMR

P27797. Positions 206-305.

DisProt

DP00333.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:104N.

IntAct

P27797. 9 interactions.

PTM databases

PhosphoSite

P27797.

2-D gel databases

SWISS-2DPAGE

P27797.

Aarhus/Ghent-2DPAGE

9401. IEF.

DOSAC-COBS-2DPAGE

P27797.

HSC-2DPAGE

P27797.

OGP

P27797.

PHCI-2DPAGE

P27797.

PMMA-2DPAGE

P27797.

REPRODUCTION-2DPAGE

IPI00020599.

Siena-2DPAGE

P27797.

Proteomic databases

PRIDE

P27797.

Genome annotation databases

Ensembl

ENSG00000179218. Homo sapiens. [Contig view]

GeneID

811.

KEGG

hsa:811.

UCSC

uc002mvu.1. human.

Organism-specific databases

GeneCards

GC19P012910.

H-InvDB

HIX0014813.

HGNC

HGNC:1455. CALR.

HPA

CAB001513.
HPA002242.

MIM

109091. gene.

PharmGKB

PA26046.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P27797.

HOVERGEN

P27797.

OMA

P27797. AYKGKWI.

Gene expression databases

ArrayExpress

P27797.

Bgee

P27797.

CleanEx

HS_CALR.

GermOnline

ENSG00000179218. Homo sapiens.

Family and domain databases

InterPro

IPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009169. Calreticulin.
IPR009033. Calreticulin/calnexin_P.
IPR013320. ConA-like_subgrp.
IPR000886. ER_targeting_sequence.
[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.

ProDom

PD001866. Calret/calnex. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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 Resources

DrugBank

DB00009. Alteplase.
DB00029. Anistreplase.
DB00025. Antihemophilic Factor.
DB00015. Reteplase.
DB00031. Tenecteplase.

NextBio

3292.

SOURCE

Search...

Entry information

Entry name

CALR_HUMAN

Accession

Primary (citable) accession number: P27797

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	July 7, 2009
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)