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Protein

Calreticulin

Gene

CALR

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi26 – 261Calcium; via carbonyl oxygenBy similarity
Metal bindingi62 – 621Calcium; via carbonyl oxygenBy similarity
Metal bindingi64 – 641Calcium; via carbonyl oxygenBy similarity
Binding sitei109 – 1091CarbohydrateBy similarity
Binding sitei111 – 1111CarbohydrateBy similarity
Binding sitei128 – 1281CarbohydrateBy similarity
Binding sitei135 – 1351CarbohydrateBy similarity
Binding sitei317 – 3171CarbohydrateBy similarity
Metal bindingi328 – 3281CalciumBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Ligandi

Calcium, Lectin, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Calreticulin
Alternative name(s):
CRP55
Calregulin
Endoplasmic reticulum resident protein 60
Short name:
ERp60
HACBP
Gene namesi
Name:CALR
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
ProteomesiUP000001811 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Sarcoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi170 – 1701H → A: Loss of activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 17172 PublicationsAdd
BLAST
Chaini18 – 418401CalreticulinPRO_0000004176Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481N6-acetyllysineBy similarity
Disulfide bondi105 ↔ 137By similarity
Modified residuei159 – 1591N6-acetyllysineBy similarity
Modified residuei209 – 2091N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

PRIDEiP15253.

Interactioni

Subunit structurei

Monomer. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interacts with GABARAP, NR3C1, PDIA3/ERp57 and TRIM21. Interacts with PPIB and C9orf9 homolog (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050673EBI-9005200,EBI-77613From a different organism.
AppP120232EBI-9005200,EBI-78814From a different organism.

Protein-protein interaction databases

BioGridi1172073. 1 interaction.
IntActiP15253. 4 interactions.

Structurei

3D structure databases

ProteinModelPortaliP15253.
SMRiP15253. Positions 206-305.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati191 – 202121-1Add
BLAST
Repeati210 – 221121-2Add
BLAST
Repeati227 – 238121-3Add
BLAST
Repeati244 – 255121-4Add
BLAST
Repeati259 – 269112-1Add
BLAST
Repeati273 – 283112-2Add
BLAST
Repeati287 – 297112-3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni18 – 197180N-domainAdd
BLAST
Regioni191 – 255654 X approximate repeatsAdd
BLAST
Regioni198 – 308111P-domainAdd
BLAST
Regioni237 – 27034Interaction with PPIBBy similarityAdd
BLAST
Regioni259 – 297393 X approximate repeatsAdd
BLAST
Regioni309 – 418110C-domainAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi415 – 4184Prevents secretion from ER

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi351 – 40858Asp/Glu/Lys-richAdd
BLAST

Domaini

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).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.
Associates with PDIA3 through the tip of the extended arm formed by the P-domain.By similarity

Sequence similaritiesi

Belongs to the calreticulin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

HOVERGENiHBG005407.
InParanoidiP15253.
KOiK08057.

Family and domain databases

Gene3Di2.60.120.200. 2 hits.
InterProiIPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009169. Calreticulin.
IPR009033. Calreticulin/calnexin_P_dom.
IPR013320. ConA-like_dom.
[Graphical view]
PANTHERiPTHR11073. PTHR11073. 1 hit.
PfamiPF00262. Calreticulin. 1 hit.
[Graphical view]
PIRSFiPIRSF002356. Calreticulin. 1 hit.
PRINTSiPR00626. CALRETICULIN.
SUPFAMiSSF49899. SSF49899. 1 hit.
SSF63887. SSF63887. 1 hit.
PROSITEiPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00805. CALRETICULIN_REPEAT. 3 hits.
PS00014. ER_TARGET. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P15253-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLPVPLLLG LLGLAAAEPV VYFKEQFLDG DGWTERWIES KHKSDFGKFV
60 70 80 90 100
LSSGKFYGDQ EKDKGLQTSQ DARFYALSAR FEPFSNKGQP LVVQFTVKHE
110 120 130 140 150
QNIDCGGGYV KLFPAGLDQK DMHGDSEYNI MFGPDICGPG TKKVHVIFNY
160 170 180 190 200
KGKNVLINKD IRCKDDEFTH LYTLIVRPDN TYEVKIDNSQ VESGSLEDDW
210 220 230 240 250
DFLPPKKIKD PDASKPEDWD ERAKIDDPTD SKPEDWDKPE HIPDPDAKKP
260 270 280 290 300
EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS
310 320 330 340 350
PDANIYAYDS FAVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT
360 370 380 390 400
KTAEKQMKDK QDEEQRLKEE EEEKKRKEEE EAEEDEEDKD DKEDEDEDEE
410
DKDEEEEEAA AGQAKDEL
Length:418
Mass (Da):48,275
Last modified:April 1, 1990 - v1
Checksum:iB6082B689DC763A6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti90 – 901P → T AA sequence (PubMed:1911780).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti35 – 351E → D.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05138 mRNA. Translation: AAA31188.1.
PIRiA34154.
C33208.
D33208.
S13046.
RefSeqiNP_001075704.1. NM_001082235.1.
UniGeneiOcu.1840.

Genome annotation databases

GeneIDi100009050.
KEGGiocu:100009050.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05138 mRNA. Translation: AAA31188.1.
PIRiA34154.
C33208.
D33208.
S13046.
RefSeqiNP_001075704.1. NM_001082235.1.
UniGeneiOcu.1840.

3D structure databases

ProteinModelPortaliP15253.
SMRiP15253. Positions 206-305.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1172073. 1 interaction.
IntActiP15253. 4 interactions.

Proteomic databases

PRIDEiP15253.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009050.
KEGGiocu:100009050.

Organism-specific databases

CTDi811.

Phylogenomic databases

HOVERGENiHBG005407.
InParanoidiP15253.
KOiK08057.

Family and domain databases

Gene3Di2.60.120.200. 2 hits.
InterProiIPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009169. Calreticulin.
IPR009033. Calreticulin/calnexin_P_dom.
IPR013320. ConA-like_dom.
[Graphical view]
PANTHERiPTHR11073. PTHR11073. 1 hit.
PfamiPF00262. Calreticulin. 1 hit.
[Graphical view]
PIRSFiPIRSF002356. Calreticulin. 1 hit.
PRINTSiPR00626. CALRETICULIN.
SUPFAMiSSF49899. SSF49899. 1 hit.
SSF63887. SSF63887. 1 hit.
PROSITEiPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00805. CALRETICULIN_REPEAT. 3 hits.
PS00014. ER_TARGET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-170.

Entry informationi

Entry nameiCALR_RABIT
AccessioniPrimary (citable) accession number: P15253
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: March 4, 2015
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.