RCN3_MOUSE
ID RCN3_MOUSE Reviewed; 328 AA.
AC Q8BH97; Q58E50; Q8R137; Q99K35; Q9CTD4;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Reticulocalbin-3 {ECO:0000305};
DE Flags: Precursor;
GN Name=Rcn3 {ECO:0000312|MGI:MGI:1277122}; Synonyms=D7Ertd671e;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, Czech II, and FVB/N; TISSUE=Colon, and Mammary gland;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Liver, Lung, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=26252542; DOI=10.1165/rcmb.2015-0036oc;
RA Jin J., Li Y., Ren J., Man Lam S., Zhang Y., Hou Y., Zhang X., Xu R.,
RA Shui G., Ma R.Z.;
RT "Neonatal Respiratory Failure with Retarded Perinatal Lung Maturation in
RT Mice Caused by Reticulocalbin 3 Disruption.";
RL Am. J. Respir. Cell Mol. Biol. 54:410-423(2016).
CC -!- FUNCTION: Probable molecular chaperone assisting protein biosynthesis
CC and transport in the endoplasmic reticulum (PubMed:26252542). Required
CC for the proper biosynthesis and transport of pulmonary surfactant-
CC associated protein A/SP-A, pulmonary surfactant-associated protein
CC D/SP-D and the lipid transporter ABCA3 (PubMed:26252542). By regulating
CC both the proper expression and the degradation through the endoplasmic
CC reticulum-associated protein degradation pathway of these proteins
CC plays a crucial role in pulmonary surfactant homeostasis
CC (PubMed:26252542). Has an anti-fibrotic activity by negatively
CC regulating the secretion of type I and type III collagens (By
CC similarity). This calcium-binding protein also transiently associates
CC with immature PCSK6 and regulates its secretion (By similarity).
CC {ECO:0000250|UniProtKB:Q96D15, ECO:0000269|PubMed:26252542}.
CC -!- SUBUNIT: Interacts with PCSK6 (immature form including the propeptide);
CC probably involved in the maturation and the secretion of PCSK6.
CC {ECO:0000250|UniProtKB:Q96D15}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:26252542}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lung and heart. Also detected
CC in liver, spleen, kidney, skeletal muscle, intestine, stomach, and
CC brain. {ECO:0000269|PubMed:26252542}.
CC -!- DEVELOPMENTAL STAGE: During lung development the expression is detected
CC from 15.5 dpc to P1 with a maximum at 17.5 dpc which corresponds to the
CC stage of development of alveolar saccules.
CC {ECO:0000269|PubMed:26252542}.
CC -!- PTM: Degraded by PCSK6 and other endoproteases including FURIN and
CC PCSK5. {ECO:0000250|UniProtKB:Q96D15}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:I6L9G5}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice show neonatal lethality
CC (PubMed:26252542). Normally delivered newborn mice exhibit normal gross
CC morphology, early motor activity, and response to painful stimuli
CC (PubMed:26252542). They quickly develop severe respiratory distress
CC with gasping and cyanosis, and die within 20 to 60 minutes after birth
CC (PubMed:26252542). Normally developed trachea and diaphragm structure
CC as well as no obvious gross morphological or histological abnormalities
CC in the heart, brain, or liver suggest that abnormal lung development is
CC the primary cause for the neonatal lethality (PubMed:26252542). Mutant
CC mice exhibit morphological abnormalities of the lungs, including
CC atelectasis with collapse of the alveolar space and unexpanded intra-
CC alveolar septae (PubMed:26252542). This is associated with an impaired
CC maturation of type 2 alveolar epithelial cells which is probably due to
CC their failure to properly produce pulmonary surfactant
CC (PubMed:26252542). {ECO:0000269|PubMed:26252542}.
CC -!- SIMILARITY: Belongs to the CREC family. {ECO:0000305}.
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DR EMBL; AK003918; BAB23076.1; -; mRNA.
DR EMBL; AK077943; BAC37077.1; -; mRNA.
DR EMBL; AK082762; BAC38608.1; -; mRNA.
DR EMBL; BC005487; AAH05487.1; -; mRNA.
DR EMBL; BC025602; AAH25602.1; -; mRNA.
DR EMBL; BC055903; AAH55903.1; -; mRNA.
DR EMBL; BC092069; AAH92069.1; -; mRNA.
DR CCDS; CCDS21229.1; -.
DR RefSeq; NP_080831.2; NM_026555.2.
DR RefSeq; XP_006541049.1; XM_006540986.2.
DR RefSeq; XP_006541050.1; XM_006540987.2.
DR AlphaFoldDB; Q8BH97; -.
DR BioGRID; 206549; 5.
DR IntAct; Q8BH97; 1.
DR STRING; 10090.ENSMUSP00000019683; -.
DR GlyConnect; 2680; 2 N-Linked glycans (1 site).
DR GlyGen; Q8BH97; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q8BH97; -.
DR PhosphoSitePlus; Q8BH97; -.
DR EPD; Q8BH97; -.
DR jPOST; Q8BH97; -.
DR MaxQB; Q8BH97; -.
DR PaxDb; Q8BH97; -.
DR PeptideAtlas; Q8BH97; -.
DR PRIDE; Q8BH97; -.
DR ProteomicsDB; 255172; -.
DR Antibodypedia; 53458; 102 antibodies from 20 providers.
DR DNASU; 52377; -.
DR Ensembl; ENSMUST00000019683; ENSMUSP00000019683; ENSMUSG00000019539.
DR Ensembl; ENSMUST00000211352; ENSMUSP00000148227; ENSMUSG00000019539.
DR GeneID; 52377; -.
DR KEGG; mmu:52377; -.
DR UCSC; uc009gta.3; mouse.
DR CTD; 57333; -.
DR MGI; MGI:1277122; Rcn3.
DR VEuPathDB; HostDB:ENSMUSG00000019539; -.
DR eggNOG; KOG4223; Eukaryota.
DR GeneTree; ENSGT01010000222360; -.
DR HOGENOM; CLU_044718_0_1_1; -.
DR InParanoid; Q8BH97; -.
DR OMA; QVEMKQI; -.
DR OrthoDB; 909079at2759; -.
DR PhylomeDB; Q8BH97; -.
DR TreeFam; TF314849; -.
DR BioGRID-ORCS; 52377; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Rcn3; mouse.
DR PRO; PR:Q8BH97; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8BH97; protein.
DR Bgee; ENSMUSG00000019539; Expressed in vault of skull and 209 other tissues.
DR ExpressionAtlas; Q8BH97; baseline and differential.
DR Genevisible; Q8BH97; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0032964; P:collagen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0036503; P:ERAD pathway; IMP:UniProtKB.
DR GO; GO:0060428; P:lung epithelium development; IMP:UniProtKB.
DR GO; GO:0055091; P:phospholipid homeostasis; IMP:UniProtKB.
DR GO; GO:0010952; P:positive regulation of peptidase activity; ISS:UniProtKB.
DR GO; GO:0009306; P:protein secretion; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IMP:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0043129; P:surfactant homeostasis; IMP:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13202; EF-hand_5; 2.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS00018; EF_HAND_1; 4.
DR PROSITE; PS50222; EF_HAND_2; 6.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Calcium; Chaperone; Endoplasmic reticulum; Glycoprotein; Metal-binding;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..328
FT /note="Reticulocalbin-3"
FT /id="PRO_0000004152"
FT DOMAIN 77..112
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 113..148
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 163..198
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 200..235
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 241..276
FT /note="EF-hand 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 277..312
FT /note="EF-hand 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 24..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 325..328
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT COMPBIAS 28..48
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 92
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 94
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 96
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 101
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 128
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 132
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 137
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 182
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 215
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 217
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 224
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 256
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 260
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 265
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 290
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 294
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 296
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 121
FT /note="A -> R (in Ref. 1; BAB23076)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="R -> Q (in Ref. 2; AAH05487)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 328 AA; 38002 MW; 3DF05C6F0D5A6314 CRC64;
MMWRWSFLLL LLLLRHWALG KPSPDAGPHG QDRVHHGTPL SEAPHDDAHG NFQYDHEAFL
GRDVAKEFDK LSPEESQARL GRIVDRMDLA GDSDGWVSLA ELRAWIAHTQ QRHIRDSVSA
AWHTYDTDRD GRVGWEELRN ATYGHYEPGE EFHDVEDAET YKKMLARDER RFRVADQDGD
SMATREELTA FLHPEEFPHM RDIVVAETLE DLDKNKDGYV QVEEYIADLY SEEPGEEEPA
WVQTERQQFR EFRDLNKDGR LDGSEVGYWV LPPSQDQPLV EANHLLHESD TDKDGRLSKA
EILSNWNMFV GSQATNYGED LTRHHDEL
