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Q96L12 (CALR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calreticulin-3
Alternative name(s):
Calreticulin-2
Calsperin
Gene names
Name:CALR3
Synonyms:CRT2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length384 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Subunit structure

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

Subcellular location

Endoplasmic reticulum lumen Ref.1.

Tissue specificity

Testis specific. Ref.6

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.

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.

Involvement in disease

Cardiomyopathy, familial hypertrophic 19 (CMH19) [MIM:613875]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the calreticulin family.

Ontologies

Keywords
   Biological processDifferentiation
Spermatogenesis
   Cellular componentEndoplasmic reticulum
   Coding sequence diversityPolymorphism
   DiseaseCardiomyopathy
Disease mutation
   DomainRepeat
Signal
   LigandLectin
Metal-binding
Zinc
   Molecular functionChaperone
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

protein folding

Inferred from electronic annotation. Source: InterPro

spermatogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentendoplasmic reticulum lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 384365Calreticulin-3
PRO_0000004178

Regions

Repeat191 – 202121-1
Repeat208 – 219121-2
Repeat221 – 230101-3
Repeat234 – 245121-4
Repeat249 – 259112-1
Repeat263 – 27192-2
Repeat273 – 283112-3
Region20 – 197178N-domain
Region191 – 245554 X approximate repeats
Region198 – 29497P-domain
Region249 – 283353 X approximate repeats
Region295 – 38490C-domain
Motif381 – 3844Prevents secretion from ER Potential
Compositional bias337 – 36226Glu/Lys-rich

Sites

Binding site1091Carbohydrate By similarity
Binding site1111Carbohydrate By similarity
Binding site1281Carbohydrate By similarity
Binding site1351Carbohydrate By similarity
Binding site3031Carbohydrate By similarity

Amino acid modifications

Glycosylation421N-linked (GlcNAc...) Potential
Glycosylation2011N-linked (GlcNAc...) Potential
Disulfide bond105 ↔ 137 By similarity

Natural variations

Natural variant81L → F. Ref.5
Corresponds to variant rs11544148 [ dbSNP | Ensembl ].
VAR_027944
Natural variant821K → R in CMH19. Ref.7
VAR_065476
Natural variant2481D → G.
Corresponds to variant rs10411092 [ dbSNP | Ensembl ].
VAR_027945
Natural variant2741V → I.
Corresponds to variant rs12459238 [ dbSNP | Ensembl ].
VAR_027946
Natural variant2841D → N.
Corresponds to variant rs10404156 [ dbSNP | Ensembl ].
VAR_048589

Sequences

Sequence LengthMass (Da)Tools
Q96L12 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 32D8AFB23D1DF7C5

FASTA38444,996
        10         20         30         40         50         60 
MARALVQLWA ICMLRVALAT VYFQEEFLDG EHWRNRWLQS TNDSRFGHFR LSSGKFYGHK 

        70         80         90        100        110        120 
EKDKGLQTTQ NGRFYAISAR FKPFSNKGKT LVIQYTVKHE QKMDCGGGYI KVFPADIDQK 

       130        140        150        160        170        180 
NLNGKSQYYI MFGPDICGFD IKKVHVILHF KNKYHENKKL IRCKVDGFTH LYTLILRPDL 

       190        200        210        220        230        240 
SYDVKIDGQS IESGSIEYDW NLTSLKKETS PAESKDWEQT KDNKAQDWEK HFLDASTSKQ 

       250        260        270        280        290        300 
SDWNGDLDGD WPAPMLQKPP YQDGLKPEGI HKDVWLHRKM KNTDYLTQYD LSEFENIGAI 

       310        320        330        340        350        360 
GLELWQVRSG TIFDNFLITD DEEYADNFGK ATWGETKGPE REMDAIQAKE EMKKAREEEE 

       370        380 
EELLSGKINR HEHYFNQFHR RNEL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS12344.1.
RefSeqNP_659483.2. NM_145046.4.
UniGeneHs.304020.

3D structure databases

ProteinModelPortalQ96L12.
SMRQ96L12. Positions 21-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125941. 1 interaction.
STRING9606.ENSP00000269881.

PTM databases

PhosphoSiteQ96L12.

Polymorphism databases

DMDM116241279.

Proteomic databases

PaxDbQ96L12.
PRIDEQ96L12.

Protocols and materials databases

DNASU125972.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269881; ENSP00000269881; ENSG00000269058.
GeneID125972.
KEGGhsa:125972.
UCSCuc002ned.3. human.

Organism-specific databases

CTD125972.
GeneCardsGC19M016589.
H-InvDBHIX0080124.
HGNCHGNC:20407. CALR3.
HPACAB025749.
HPA043355.
HPA048460.
MIM611414. gene.
613875. phenotype.
neXtProtNX_Q96L12.
Orphanet155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA134922944.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG268919.
HOGENOMHOG000192435.
HOVERGENHBG005407.
InParanoidQ96L12.
KOK10098.
OMAQDWEKHF.
OrthoDBEOG77126Z.
PhylomeDBQ96L12.
TreeFamTF338438.

Gene expression databases

BgeeQ96L12.
CleanExHS_CALR3.
GenevestigatorQ96L12.

Family and domain databases

Gene3D2.60.120.200. 1 hit.
InterProIPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009169. Calreticulin.
IPR009033. Calreticulin/calnexin_P_dom.
IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
[Graphical view]
PANTHERPTHR11073. PTHR11073. 1 hit.
PfamPF00262. Calreticulin. 1 hit.
[Graphical view]
PIRSFPIRSF002356. Calreticulin. 1 hit.
PRINTSPR00626. CALRETICULIN.
SUPFAMSSF49899. SSF49899. 2 hits.
SSF63887. SSF63887. 1 hit.
PROSITEPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00014. ER_TARGET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi125972.
NextBio81602.
PROQ96L12.
SOURCESearch...

Entry information

Entry nameCALR3_HUMAN
AccessionPrimary (citable) accession number: Q96L12
Secondary accession number(s): D9N574, Q96LN3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM