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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei109 – 1091CarbohydrateBy similarity
Binding sitei111 – 1111CarbohydrateBy similarity
Binding sitei128 – 1281CarbohydrateBy similarity
Binding sitei135 – 1351CarbohydrateBy similarity
Binding sitei303 – 3031CarbohydrateBy similarity

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. carbohydrate binding Source: UniProtKB-KW

GO - Biological processi

  1. cell differentiation Source: UniProtKB-KW
  2. protein folding Source: InterPro
  3. spermatogenesis Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

Differentiation, Spermatogenesis

Keywords - Ligandi

Lectin, Metal-binding, Zinc

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
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:20407. CALR3.

Subcellular locationi

  1. Endoplasmic reticulum lumen PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. endoplasmic reticulum lumen Source: UniProtKB-SubCell
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti82 – 821K → R in CMH19. 1 Publication
VAR_065476

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

MIMi613875. phenotype.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA134922944.

Polymorphism and mutation databases

BioMutaiCALR3.
DMDMi116241279.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Chaini20 – 384365Calreticulin-3PRO_0000004178Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi105 ↔ 137By similarity
Glycosylationi201 – 2011N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ96L12.
PRIDEiQ96L12.

PTM databases

PhosphoSiteiQ96L12.

Expressioni

Tissue specificityi

Testis specific.1 Publication

Gene expression databases

BgeeiQ96L12.
CleanExiHS_CALR3.
GenevestigatoriQ96L12.

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. 8 interactions.
STRINGi9606.ENSP00000269881.

Structurei

3D structure databases

ProteinModelPortaliQ96L12.
SMRiQ96L12. Positions 21-351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati191 – 202121-1Add
BLAST
Repeati208 – 219121-2Add
BLAST
Repeati221 – 230101-3
Repeati234 – 245121-4Add
BLAST
Repeati249 – 259112-1Add
BLAST
Repeati263 – 27192-2
Repeati273 – 283112-3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni20 – 197178N-domainAdd
BLAST
Regioni191 – 245554 X approximate repeatsAdd
BLAST
Regioni198 – 29497P-domainAdd
BLAST
Regioni249 – 283353 X approximate repeatsAdd
BLAST
Regioni295 – 38490C-domainAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi381 – 3844Prevents secretion from ERPROSITE-ProRule annotation

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi337 – 36226Glu/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.By similarity

Sequence similaritiesi

Belongs to the calreticulin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG268919.
GeneTreeiENSGT00430000030841.
HOGENOMiHOG000192435.
HOVERGENiHBG005407.
InParanoidiQ96L12.
KOiK10098.
OMAiQDWEKHF.
OrthoDBiEOG77126Z.
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. 1 hit.
[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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti8 – 81L → F.1 Publication
Corresponds to variant rs11544148 [ dbSNP | Ensembl ].
VAR_027944
Natural varianti82 – 821K → R in CMH19. 1 Publication
VAR_065476
Natural varianti248 – 2481D → G.
Corresponds to variant rs10411092 [ dbSNP | Ensembl ].
VAR_027945
Natural varianti274 – 2741V → I.
Corresponds to variant rs12459238 [ dbSNP | Ensembl ].
VAR_027946
Natural varianti284 – 2841D → N.
Corresponds to variant rs10404156 [ dbSNP | Ensembl ].
VAR_048589

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.

Polymorphism and mutation databases

BioMutaiCALR3.

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.
SMRiQ96L12. Positions 21-351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125941. 8 interactions.
STRINGi9606.ENSP00000269881.

PTM databases

PhosphoSiteiQ96L12.

Polymorphism and mutation databases

BioMutaiCALR3.
DMDMi116241279.

Proteomic databases

PaxDbiQ96L12.
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.
GeneCardsiGC19M016589.
H-InvDBHIX0080124.
HGNCiHGNC:20407. CALR3.
HPAiCAB025749.
HPA043355.
HPA048460.
MIMi611414. gene.
613875. phenotype.
neXtProtiNX_Q96L12.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA134922944.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG268919.
GeneTreeiENSGT00430000030841.
HOGENOMiHOG000192435.
HOVERGENiHBG005407.
InParanoidiQ96L12.
KOiK10098.
OMAiQDWEKHF.
OrthoDBiEOG77126Z.
PhylomeDBiQ96L12.
TreeFamiTF338438.

Miscellaneous databases

GenomeRNAii125972.
NextBioi81602.
PROiQ96L12.
SOURCEiSearch...

Gene expression databases

BgeeiQ96L12.
CleanExiHS_CALR3.
GenevestigatoriQ96L12.

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. 1 hit.
[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...

Publicationsi

« Hide 'large scale' publications
  1. "Calreticulin-2 is localized in the lumen of the endoplasmic reticulum but is not a Ca2+ -binding protein."
    Nomura R., Orii M., Senda T.
    Histochem. Cell Biol. 135:531-538(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, LACK OF CALCIUM-BINDING.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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], VARIANT PHE-8.
    Tissue: Testis.
  6. "Identification of a novel calreticulin isoform (Crt2) in human and mouse."
    Persson S., Rosenquist M., Sommarin M.
    Gene 297:151-158(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION, TISSUE SPECIFICITY.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  8. "Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy."
    Chiu C., Tebo M., Ingles J., Yeates L., Arthur J.W., Lind J.M., Semsarian C.
    J. Mol. Cell. Cardiol. 43:337-343(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMH19 ARG-82.

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: April 29, 2015
This is version 131 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

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.