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Protein

Calreticulin-3

Gene

CALR3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3. Required for sperm fertility (By similarity). CALR3 capacity for calcium-binding may be absent or much lower than that of CALR.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei109CarbohydrateBy similarity1
Binding sitei111CarbohydrateBy similarity1
Binding sitei128CarbohydrateBy similarity1
Binding sitei135CarbohydrateBy similarity1
Binding sitei303CarbohydrateBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

Differentiation, Spermatogenesis

Keywords - Ligandi

Lectin, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141979-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Calreticulin-3
Alternative name(s):
Calreticulin-2
Calsperin
Gene namesi
Name:CALR3
Synonyms:CRT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:20407. CALR3.

Subcellular locationi

  • Endoplasmic reticulum lumen PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic 19 (CMH19)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
See also OMIM:613875
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06547682K → R in CMH19. 1 PublicationCorresponds to variant rs142951029dbSNPEnsembl.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi125972.
MalaCardsiCALR3.
MIMi613875. phenotype.
OpenTargetsiENSG00000269058.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA134922944.

Polymorphism and mutation databases

BioMutaiCALR3.
DMDMi116241279.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000000417820 – 384Calreticulin-3Add BLAST365

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi42N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi105 ↔ 137By similarity
Glycosylationi201N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ96L12.
PeptideAtlasiQ96L12.
PRIDEiQ96L12.

PTM databases

iPTMnetiQ96L12.
PhosphoSitePlusiQ96L12.

Expressioni

Tissue specificityi

Testis specific.1 Publication

Gene expression databases

BgeeiENSG00000269058.
CleanExiHS_CALR3.
ExpressionAtlasiQ96L12. baseline and differential.
GenevisibleiQ96L12. HS.

Organism-specific databases

HPAiCAB025749.
HPA043355.
HPA048460.

Interactioni

Subunit structurei

Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5.By similarity

Protein-protein interaction databases

BioGridi125941. 11 interactors.
STRINGi9606.ENSP00000269881.

Structurei

3D structure databases

ProteinModelPortaliQ96L12.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati191 – 2021-1Add BLAST12
Repeati208 – 2191-2Add BLAST12
Repeati221 – 2301-310
Repeati234 – 2451-4Add BLAST12
Repeati249 – 2592-1Add BLAST11
Repeati263 – 2712-29
Repeati273 – 2832-3Add BLAST11

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 197N-domainAdd BLAST178
Regioni191 – 2454 X approximate repeatsAdd BLAST55
Regioni198 – 294P-domainAdd BLAST97
Regioni249 – 2833 X approximate repeatsAdd BLAST35
Regioni295 – 384C-domainAdd BLAST90

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi381 – 384Prevents secretion from ERPROSITE-ProRule annotation4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi337 – 362Glu/Lys-richAdd BLAST26

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.By similarity

Sequence similaritiesi

Belongs to the calreticulin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG0674. Eukaryota.
ENOG410XRR7. LUCA.
GeneTreeiENSGT00430000030841.
HOGENOMiHOG000192435.
HOVERGENiHBG005407.
InParanoidiQ96L12.
KOiK10098.
OMAiWVQSTND.
OrthoDBiEOG091G0AP1.
PhylomeDBiQ96L12.
TreeFamiTF338438.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
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. 2 hits.
[Graphical view]
PIRSFiPIRSF002356. Calreticulin. 1 hit.
PRINTSiPR00626. CALRETICULIN.
SUPFAMiSSF49899. SSF49899. 2 hits.
SSF63887. SSF63887. 1 hit.
PROSITEiPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00014. ER_TARGET. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q96L12-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARALVQLWA ICMLRVALAT VYFQEEFLDG EHWRNRWLQS TNDSRFGHFR
60 70 80 90 100
LSSGKFYGHK EKDKGLQTTQ NGRFYAISAR FKPFSNKGKT LVIQYTVKHE
110 120 130 140 150
QKMDCGGGYI KVFPADIDQK NLNGKSQYYI MFGPDICGFD IKKVHVILHF
160 170 180 190 200
KNKYHENKKL IRCKVDGFTH LYTLILRPDL SYDVKIDGQS IESGSIEYDW
210 220 230 240 250
NLTSLKKETS PAESKDWEQT KDNKAQDWEK HFLDASTSKQ SDWNGDLDGD
260 270 280 290 300
WPAPMLQKPP YQDGLKPEGI HKDVWLHRKM KNTDYLTQYD LSEFENIGAI
310 320 330 340 350
GLELWQVRSG TIFDNFLITD DEEYADNFGK ATWGETKGPE REMDAIQAKE
360 370 380
EMKKAREEEE EELLSGKINR HEHYFNQFHR RNEL
Length:384
Mass (Da):44,996
Last modified:October 17, 2006 - v2
Checksum:i32D8AFB23D1DF7C5
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0279448L → F.1 PublicationCorresponds to variant rs11544148dbSNPEnsembl.1
Natural variantiVAR_06547682K → R in CMH19. 1 PublicationCorresponds to variant rs142951029dbSNPEnsembl.1
Natural variantiVAR_027945248D → G.Corresponds to variant rs10411092dbSNPEnsembl.1
Natural variantiVAR_027946274V → I.Corresponds to variant rs12459238dbSNPEnsembl.1
Natural variantiVAR_048589284D → N.Corresponds to variant rs10404156dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB576176 mRNA. Translation: BAJ14705.1.
AK058084 mRNA. Translation: BAB71655.1.
AC008764 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84546.1.
BC014595 mRNA. Translation: AAH14595.1.
CCDSiCCDS12344.1.
RefSeqiNP_659483.2. NM_145046.4.
UniGeneiHs.304020.

Genome annotation databases

EnsembliENST00000269881; ENSP00000269881; ENSG00000269058.
GeneIDi125972.
KEGGihsa:125972.
UCSCiuc002ned.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB576176 mRNA. Translation: BAJ14705.1.
AK058084 mRNA. Translation: BAB71655.1.
AC008764 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84546.1.
BC014595 mRNA. Translation: AAH14595.1.
CCDSiCCDS12344.1.
RefSeqiNP_659483.2. NM_145046.4.
UniGeneiHs.304020.

3D structure databases

ProteinModelPortaliQ96L12.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125941. 11 interactors.
STRINGi9606.ENSP00000269881.

PTM databases

iPTMnetiQ96L12.
PhosphoSitePlusiQ96L12.

Polymorphism and mutation databases

BioMutaiCALR3.
DMDMi116241279.

Proteomic databases

PaxDbiQ96L12.
PeptideAtlasiQ96L12.
PRIDEiQ96L12.

Protocols and materials databases

DNASUi125972.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269881; ENSP00000269881; ENSG00000269058.
GeneIDi125972.
KEGGihsa:125972.
UCSCiuc002ned.3. human.

Organism-specific databases

CTDi125972.
DisGeNETi125972.
GeneCardsiCALR3.
H-InvDBHIX0080124.
HGNCiHGNC:20407. CALR3.
HPAiCAB025749.
HPA043355.
HPA048460.
MalaCardsiCALR3.
MIMi611414. gene.
613875. phenotype.
neXtProtiNX_Q96L12.
OpenTargetsiENSG00000269058.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA134922944.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0674. Eukaryota.
ENOG410XRR7. LUCA.
GeneTreeiENSGT00430000030841.
HOGENOMiHOG000192435.
HOVERGENiHBG005407.
InParanoidiQ96L12.
KOiK10098.
OMAiWVQSTND.
OrthoDBiEOG091G0AP1.
PhylomeDBiQ96L12.
TreeFamiTF338438.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141979-MONOMER.

Miscellaneous databases

GenomeRNAii125972.
PROiQ96L12.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000269058.
CleanExiHS_CALR3.
ExpressionAtlasiQ96L12. baseline and differential.
GenevisibleiQ96L12. HS.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
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. 2 hits.
[Graphical view]
PIRSFiPIRSF002356. Calreticulin. 1 hit.
PRINTSiPR00626. CALRETICULIN.
SUPFAMiSSF49899. SSF49899. 2 hits.
SSF63887. SSF63887. 1 hit.
PROSITEiPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00014. ER_TARGET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCALR3_HUMAN
AccessioniPrimary (citable) accession number: Q96L12
Secondary accession number(s): D9N574, Q96LN3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.