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 28-JAN-2026, entry version 196. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_145046.5. DR AlphaFoldDB; Q96L12; -. DR SMR; Q96L12; -. DR BioGRID; 125941; 141. DR FunCoup; Q96L12; 228. DR IntAct; Q96L12; 17. DR MINT; Q96L12; -. DR STRING; 9606.ENSP00000269881; -. DR DrugBank; DB11093; Calcium citrate. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR GlyCosmos; Q96L12; 2 sites, No reported glycans. DR GlyGen; Q96L12; 2 sites. DR iPTMnet; Q96L12; -. DR PhosphoSitePlus; Q96L12; -. DR BioMuta; CALR3; -. DR DMDM; 116241279; -. DR jPOST; Q96L12; -. DR MassIVE; Q96L12; -. DR PaxDb; 9606-ENSP00000269881; -. DR PeptideAtlas; Q96L12; -. DR ProteomicsDB; 77137; -. DR Pumba; Q96L12; -. DR Antibodypedia; 66699; 339 antibodies from 29 providers. DR DNASU; 125972; -. DR Ensembl; ENST00000269881.8; ENSP00000269881.3; ENSG00000269058.7. 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 AGR; HGNC:20407; -. DR ClinPGx; PA134922944; -. DR CTD; 125972; -. DR DisGeNET; 125972; -. DR GeneCards; CALR3; -. DR HGNC; HGNC:20407; CALR3. DR HPA; ENSG00000269058; Tissue enriched (testis). DR MalaCards; CALR3; -. DR MIM; 611414; gene. DR OpenTargets; ENSG00000269058; -. DR VEuPathDB; HostDB:ENSG00000269058; -. DR eggNOG; KOG0674; Eukaryota. DR GeneTree; ENSGT00950000182915; -. DR HOGENOM; CLU_018224_0_0_1; -. DR InParanoid; Q96L12; -. DR OMA; HYFNRFH; -. DR OrthoDB; 1938156at2759; -. DR PAN-GO; Q96L12; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q96L12; -. DR PathwayCommons; Q96L12; -. DR SignaLink; Q96L12; -. DR Agora; ENSG00000269058; -. DR BioGRID-ORCS; 125972; 27 hits in 1143 CRISPR screens. DR CD-CODE; DEE660B4; Stress granule. 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 42 other cell types or tissues. DR ExpressionAtlas; Q96L12; baseline. 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:0036503; P:ERAD pathway; IBA:GO_Central. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW. DR FunFam; 2.60.120.200:FF:000122; Calreticulin 3; 1. DR FunFam; 2.60.120.200:FF:000339; Calreticulin 3; 1. DR Gene3D; 2.60.120.200; -; 2. 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; CALRETICULIN AND CALNEXIN; 1. DR PANTHER; PTHR11073:SF3; CALRETICULIN-3; 1. DR Pfam; PF00262; Calreticulin; 2. DR PIRSF; PIRSF002356; Calreticulin; 1. DR PRINTS; PR00626; CALRETICULIN. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF63887; P-domain of calnexin/calreticulin; 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; Disulfide bond; KW Endoplasmic reticulum; Glycoprotein; Lectin; Metal-binding; KW Proteomics identification; Reference proteome; Repeat; Signal; KW 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 (in 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 //