CALR3_HUMAN
ID CALR3_HUMAN Reviewed; 384 AA.
AC Q96L12; D9N574; Q96LN3;
DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Calreticulin-3;
DE AltName: Full=Calreticulin-2;
DE AltName: Full=Calsperin;
DE Flags: Precursor;
GN Name=CALR3; Synonyms=CRT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND LACK OF
RP CALCIUM-BINDING.
RX PubMed=21590275; DOI=10.1007/s00418-011-0817-z;
RA Nomura R., Orii M., Senda T.;
RT "Calreticulin-2 is localized in the lumen of the endoplasmic reticulum but
RT is not a Ca2+ -binding protein.";
RL Histochem. Cell Biol. 135:531-538(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-8.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RX PubMed=12384296; DOI=10.1016/s0378-1119(02)00880-6;
RA Persson S., Rosenquist M., Sommarin M.;
RT "Identification of a novel calreticulin isoform (Crt2) in human and
RT mouse.";
RL Gene 297:151-158(2002).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP VARIANT ARG-82.
RX PubMed=17655857; DOI=10.1016/j.yjmcc.2007.06.009;
RA Chiu C., Tebo M., Ingles J., Yeates L., Arthur J.W., Lind J.M.,
RA Semsarian C.;
RT "Genetic screening of calcium regulation genes in familial hypertrophic
RT cardiomyopathy.";
RL J. Mol. Cell. Cardiol. 43:337-343(2007).
CC -!- FUNCTION: During spermatogenesis, may act as a lectin-independent
CC chaperone for specific client proteins such as ADAM3. Required for
CC sperm fertility (By similarity). CALR3 capacity for calcium-binding may
CC be absent or much lower than that of CALR. {ECO:0000250,
CC ECO:0000269|PubMed:21590275}.
CC -!- SUBUNIT: Component of an EIF2 complex at least composed of
CC CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC ProRule:PRU10138, ECO:0000269|PubMed:21590275}.
CC -!- TISSUE SPECIFICITY: Testis specific. {ECO:0000269|PubMed:12384296}.
CC -!- DOMAIN: Can be divided into a N-terminal globular domain, a proline-
CC rich P-domain forming an elongated arm-like structure and a C-terminal
CC acidic domain. The P-domain binds one molecule of calcium with high
CC affinity, whereas the acidic C-domain binds multiple calcium ions with
CC low affinity (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The interaction with glycans occurs through a binding site in
CC the globular lectin domain. {ECO:0000250}.
CC -!- DOMAIN: The zinc binding sites are localized to the N-domain.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the calreticulin family. {ECO:0000305}.
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DR EMBL; AB576176; BAJ14705.1; -; mRNA.
DR EMBL; AK058084; BAB71655.1; -; mRNA.
DR EMBL; AC008764; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84546.1; -; Genomic_DNA.
DR EMBL; BC014595; AAH14595.1; -; mRNA.
DR CCDS; CCDS12344.1; -.
DR RefSeq; NP_659483.2; NM_145046.4.
DR AlphaFoldDB; Q96L12; -.
DR SMR; Q96L12; -.
DR BioGRID; 125941; 141.
DR IntAct; Q96L12; 8.
DR MINT; Q96L12; -.
DR STRING; 9606.ENSP00000269881; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR GlyGen; Q96L12; 2 sites.
DR iPTMnet; Q96L12; -.
DR PhosphoSitePlus; Q96L12; -.
DR BioMuta; CALR3; -.
DR DMDM; 116241279; -.
DR EPD; Q96L12; -.
DR MassIVE; Q96L12; -.
DR PaxDb; Q96L12; -.
DR PeptideAtlas; Q96L12; -.
DR PRIDE; Q96L12; -.
DR ProteomicsDB; 77137; -.
DR Antibodypedia; 66699; 331 antibodies from 28 providers.
DR DNASU; 125972; -.
DR Ensembl; ENST00000269881.8; ENSP00000269881.3; ENSG00000269058.6.
DR GeneID; 125972; -.
DR KEGG; hsa:125972; -.
DR MANE-Select; ENST00000269881.8; ENSP00000269881.3; NM_145046.5; NP_659483.2.
DR UCSC; uc002ned.3; human.
DR CTD; 125972; -.
DR DisGeNET; 125972; -.
DR GeneCards; CALR3; -.
DR HGNC; HGNC:20407; CALR3.
DR HPA; ENSG00000269058; Tissue enriched (testis).
DR MIM; 611414; gene.
DR neXtProt; NX_Q96L12; -.
DR OpenTargets; ENSG00000269058; -.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA134922944; -.
DR VEuPathDB; HostDB:ENSG00000269058; -.
DR eggNOG; KOG0674; Eukaryota.
DR GeneTree; ENSGT00950000182915; -.
DR HOGENOM; CLU_018224_0_0_1; -.
DR InParanoid; Q96L12; -.
DR OMA; DWPAPML; -.
DR OrthoDB; 822188at2759; -.
DR PhylomeDB; Q96L12; -.
DR TreeFam; TF338438; -.
DR PathwayCommons; Q96L12; -.
DR SignaLink; Q96L12; -.
DR BioGRID-ORCS; 125972; 19 hits in 1068 CRISPR screens.
DR GenomeRNAi; 125972; -.
DR Pharos; Q96L12; Tbio.
DR PRO; PR:Q96L12; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96L12; protein.
DR Bgee; ENSG00000269058; Expressed in right testis and 41 other tissues.
DR ExpressionAtlas; Q96L12; baseline and differential.
DR Genevisible; Q96L12; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044183; F:protein folding chaperone; IEA:Ensembl.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR InterPro; IPR001580; Calret/calnex.
DR InterPro; IPR018124; Calret/calnex_CS.
DR InterPro; IPR009169; Calreticulin.
DR InterPro; IPR009033; Calreticulin/calnexin_P_dom_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR PANTHER; PTHR11073; PTHR11073; 1.
DR Pfam; PF00262; Calreticulin; 2.
DR PIRSF; PIRSF002356; Calreticulin; 1.
DR PRINTS; PR00626; CALRETICULIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF63887; SSF63887; 1.
DR PROSITE; PS00803; CALRETICULIN_1; 1.
DR PROSITE; PS00804; CALRETICULIN_2; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Cardiomyopathy; Chaperone; Differentiation; Disease variant;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Lectin; Metal-binding;
KW Reference proteome; Repeat; Signal; Spermatogenesis; Zinc.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..384
FT /note="Calreticulin-3"
FT /id="PRO_0000004178"
FT REPEAT 191..202
FT /note="1-1"
FT REPEAT 208..219
FT /note="1-2"
FT REPEAT 221..230
FT /note="1-3"
FT REPEAT 234..245
FT /note="1-4"
FT REPEAT 249..259
FT /note="2-1"
FT REPEAT 263..271
FT /note="2-2"
FT REPEAT 273..283
FT /note="2-3"
FT REGION 20..197
FT /note="N-domain"
FT REGION 191..245
FT /note="4 X approximate repeats"
FT REGION 198..294
FT /note="P-domain"
FT REGION 249..283
FT /note="3 X approximate repeats"
FT REGION 295..384
FT /note="C-domain"
FT MOTIF 381..384
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT BINDING 109
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT BINDING 111
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT BINDING 128
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT BINDING 135
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT BINDING 303
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 105..137
FT /evidence="ECO:0000250"
FT VARIANT 8
FT /note="L -> F (in dbSNP:rs11544148)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027944"
FT VARIANT 82
FT /note="K -> R (found in a patient with hypertrophic
FT cardiomyopathy; unknown pathological significance;
FT dbSNP:rs142951029)"
FT /evidence="ECO:0000269|PubMed:17655857"
FT /id="VAR_065476"
FT VARIANT 248
FT /note="D -> G (in dbSNP:rs10411092)"
FT /id="VAR_027945"
FT VARIANT 274
FT /note="V -> I (in dbSNP:rs12459238)"
FT /id="VAR_027946"
FT VARIANT 284
FT /note="D -> N (in dbSNP:rs10404156)"
FT /id="VAR_048589"
SQ SEQUENCE 384 AA; 44996 MW; 32D8AFB23D1DF7C5 CRC64;
MARALVQLWA ICMLRVALAT VYFQEEFLDG EHWRNRWLQS TNDSRFGHFR LSSGKFYGHK
EKDKGLQTTQ NGRFYAISAR FKPFSNKGKT LVIQYTVKHE QKMDCGGGYI KVFPADIDQK
NLNGKSQYYI MFGPDICGFD IKKVHVILHF KNKYHENKKL IRCKVDGFTH LYTLILRPDL
SYDVKIDGQS IESGSIEYDW NLTSLKKETS PAESKDWEQT KDNKAQDWEK HFLDASTSKQ
SDWNGDLDGD WPAPMLQKPP YQDGLKPEGI HKDVWLHRKM KNTDYLTQYD LSEFENIGAI
GLELWQVRSG TIFDNFLITD DEEYADNFGK ATWGETKGPE REMDAIQAKE EMKKAREEEE
EELLSGKINR HEHYFNQFHR RNEL
