RCN3_HUMAN
ID RCN3_HUMAN Reviewed; 328 AA.
AC Q96D15; Q9HBZ8;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Reticulocalbin-3 {ECO:0000305};
DE AltName: Full=EF-hand calcium-binding protein RLP49;
DE Flags: Precursor;
GN Name=RCN3 {ECO:0000312|HGNC:HGNC:21145};
GN ORFNames=UNQ239/PRO272 {ECO:0000312|EMBL:AAQ88789.1};
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].
RA Liu F., Zeng L.-C., Rong Y.-P., Qi X.-F., Ma W.-J., Han Z.-G.;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-140.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION, CALCIUM-BINDING, INTERACTION WITH PCSK6, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ARG-86;
RP ARG-112 AND 325-HIS--LEU-328.
RX PubMed=16433634; DOI=10.1042/bj20051524;
RA Tsuji A., Kikuchi Y., Sato Y., Koide S., Yuasa K., Nagahama M., Matsuda Y.;
RT "A proteomic approach reveals transient association of reticulocalbin-3, a
RT novel member of the CREC family, with the precursor of subtilisin-like
RT proprotein convertase, PACE4.";
RL Biochem. J. 396:51-59(2006).
RN [8]
RP FUNCTION, AND INDUCTION BY ALDOSTERONE.
RX PubMed=28939891; DOI=10.1038/s41598-017-12305-7;
RA Martinez-Martinez E., Ibarrola J., Fernandez-Celis A., Santamaria E.,
RA Fernandez-Irigoyen J., Rossignol P., Jaisser F., Lopez-Andres N.;
RT "Differential Proteomics Identifies Reticulocalbin-3 as a Novel Negative
RT Mediator of Collagen Production in Human Cardiac Fibroblasts.";
RL Sci. Rep. 7:12192-12192(2017).
CC -!- FUNCTION: Probable molecular chaperone assisting protein biosynthesis
CC and transport in the endoplasmic reticulum (PubMed:16433634,
CC PubMed:28939891). Required for the proper biosynthesis and transport of
CC pulmonary surfactant-associated protein A/SP-A, pulmonary surfactant-
CC associated protein D/SP-D and the lipid transporter ABCA3 (By
CC similarity). By regulating both the proper expression and the
CC degradation through the endoplasmic reticulum-associated protein
CC degradation pathway of these proteins plays a crucial role in pulmonary
CC surfactant homeostasis (By similarity). Has an anti-fibrotic activity
CC by negatively regulating the secretion of type I and type III collagens
CC (PubMed:28939891). This calcium-binding protein also transiently
CC associates with immature PCSK6 and regulates its secretion
CC (PubMed:16433634). {ECO:0000250|UniProtKB:Q8BH97,
CC ECO:0000269|PubMed:16433634, ECO:0000269|PubMed:28939891}.
CC -!- SUBUNIT: Interacts with PCSK6 (immature form including the propeptide);
CC probably involved in the maturation and the secretion of PCSK6.
CC {ECO:0000269|PubMed:16433634}.
CC -!- INTERACTION:
CC Q96D15; Q8IW40: CCDC103; NbExp=3; IntAct=EBI-746283, EBI-10261970;
CC Q96D15; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-746283, EBI-14103818;
CC Q96D15; O95983: MBD3; NbExp=3; IntAct=EBI-746283, EBI-1783068;
CC Q96D15; O95983-2: MBD3; NbExp=3; IntAct=EBI-746283, EBI-11978579;
CC Q96D15; P41227: NAA10; NbExp=3; IntAct=EBI-746283, EBI-747693;
CC Q96D15; Q8N7B6: PACRGL; NbExp=3; IntAct=EBI-746283, EBI-3925298;
CC Q96D15; Q9UMX1: SUFU; NbExp=5; IntAct=EBI-746283, EBI-740595;
CC Q96D15; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-746283, EBI-740727;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:16433634}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16433634}.
CC -!- INDUCTION: Down-regulated by aldosterone (at protein level). No effect
CC at the transcript level. {ECO:0000269|PubMed:28939891}.
CC -!- PTM: Degraded by PCSK6 and other endoproteases including FURIN and
CC PCSK5. {ECO:0000269|PubMed:16433634}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:I6L9G5}.
CC -!- SIMILARITY: Belongs to the CREC family. {ECO:0000305}.
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DR EMBL; AY195859; AAO43054.1; -; mRNA.
DR EMBL; AF183423; AAG09692.1; -; mRNA.
DR EMBL; AY358423; AAQ88789.1; -; mRNA.
DR EMBL; BC013436; AAH13436.1; -; mRNA.
DR CCDS; CCDS12771.1; -.
DR RefSeq; NP_065701.2; NM_020650.2.
DR RefSeq; XP_011525445.1; XM_011527143.1.
DR RefSeq; XP_016882512.1; XM_017027023.1.
DR AlphaFoldDB; Q96D15; -.
DR BioGRID; 121488; 19.
DR IntAct; Q96D15; 17.
DR MINT; Q96D15; -.
DR STRING; 9606.ENSP00000270645; -.
DR GlyConnect; 1713; 10 N-Linked glycans (1 site).
DR GlyGen; Q96D15; 2 sites, 10 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q96D15; -.
DR MetOSite; Q96D15; -.
DR PhosphoSitePlus; Q96D15; -.
DR BioMuta; RCN3; -.
DR DMDM; 30316268; -.
DR DOSAC-COBS-2DPAGE; Q96D15; -.
DR EPD; Q96D15; -.
DR jPOST; Q96D15; -.
DR MassIVE; Q96D15; -.
DR MaxQB; Q96D15; -.
DR PaxDb; Q96D15; -.
DR PeptideAtlas; Q96D15; -.
DR PRIDE; Q96D15; -.
DR ProteomicsDB; 76245; -.
DR Antibodypedia; 53458; 102 antibodies from 20 providers.
DR DNASU; 57333; -.
DR Ensembl; ENST00000270645.8; ENSP00000270645.2; ENSG00000142552.8.
DR GeneID; 57333; -.
DR KEGG; hsa:57333; -.
DR MANE-Select; ENST00000270645.8; ENSP00000270645.2; NM_020650.3; NP_065701.2.
DR UCSC; uc002poj.4; human.
DR CTD; 57333; -.
DR DisGeNET; 57333; -.
DR GeneCards; RCN3; -.
DR HGNC; HGNC:21145; RCN3.
DR HPA; ENSG00000142552; Low tissue specificity.
DR MIM; 619032; gene.
DR neXtProt; NX_Q96D15; -.
DR OpenTargets; ENSG00000142552; -.
DR PharmGKB; PA134880380; -.
DR VEuPathDB; HostDB:ENSG00000142552; -.
DR eggNOG; KOG4223; Eukaryota.
DR GeneTree; ENSGT01010000222360; -.
DR HOGENOM; CLU_044718_0_1_1; -.
DR InParanoid; Q96D15; -.
DR OMA; QVEMKQI; -.
DR OrthoDB; 909079at2759; -.
DR PhylomeDB; Q96D15; -.
DR TreeFam; TF314849; -.
DR PathwayCommons; Q96D15; -.
DR SignaLink; Q96D15; -.
DR BioGRID-ORCS; 57333; 11 hits in 1078 CRISPR screens.
DR ChiTaRS; RCN3; human.
DR GenomeRNAi; 57333; -.
DR Pharos; Q96D15; Tbio.
DR PRO; PR:Q96D15; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96D15; protein.
DR Bgee; ENSG00000142552; Expressed in stromal cell of endometrium and 174 other tissues.
DR ExpressionAtlas; Q96D15; baseline and differential.
DR Genevisible; Q96D15; HS.
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; IDA:HPA.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0032964; P:collagen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0036503; P:ERAD pathway; ISS:UniProtKB.
DR GO; GO:0060428; P:lung epithelium development; ISS:UniProtKB.
DR GO; GO:0055091; P:phospholipid homeostasis; ISS:UniProtKB.
DR GO; GO:0010952; P:positive regulation of peptidase activity; IMP:UniProtKB.
DR GO; GO:0009306; P:protein secretion; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; ISS:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0043129; P:surfactant homeostasis; ISS: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 Protein transport; Reference proteome; Repeat; Signal; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..328
FT /note="Reticulocalbin-3"
FT /id="PRO_0000004151"
FT DOMAIN 75..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 19..49
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 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:0000269|PubMed:19159218"
FT VARIANT 250
FT /note="R -> W (in dbSNP:rs34654230)"
FT /id="VAR_033696"
FT MUTAGEN 86
FT /note="R->K: Decreased function in PCSK6 maturation and/or
FT secretion."
FT /evidence="ECO:0000269|PubMed:16433634"
FT MUTAGEN 112
FT /note="R->K: Decreased function in PCSK6 maturation and/or
FT secretion."
FT /evidence="ECO:0000269|PubMed:16433634"
FT MUTAGEN 325..328
FT /note="Missing: Decreased function in PCSK6 maturation
FT and/or secretion."
FT /evidence="ECO:0000269|PubMed:16433634"
FT CONFLICT 82
FT /note="R -> G (in Ref. 2; AAG09692)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="G -> S (in Ref. 2; AAG09692)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 328 AA; 37493 MW; B64EDB28B9610B8D CRC64;
MMWRPSVLLL LLLLRHGAQG KPSPDAGPHG QGRVHQAAPL SDAPHDDAHG NFQYDHEAFL
GREVAKEFDQ LTPEESQARL GRIVDRMDRA GDGDGWVSLA ELRAWIAHTQ QRHIRDSVSA
AWDTYDTDRD GRVGWEELRN ATYGHYAPGE EFHDVEDAET YKKMLARDER RFRVADQDGD
SMATREELTA FLHPEEFPHM RDIVIAETLE DLDRNKDGYV QVEEYIADLY SAEPGEEEPA
WVQTERQQFR DFRDLNKDGH LDGSEVGHWV LPPAQDQPLV EANHLLHESD TDKDGRLSKA
EILGNWNMFV GSQATNYGED LTRHHDEL
