RGN_RAT
ID RGN_RAT Reviewed; 299 AA.
AC Q03336; Q63496; Q925W3; Q9QWP2;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Regucalcin;
DE Short=RC;
DE AltName: Full=Gluconolactonase;
DE Short=GNL;
DE EC=3.1.1.17;
DE AltName: Full=Senescence marker protein 30;
DE Short=SMP-30;
GN Name=Rgn; Synonyms=Smp30;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=1420310; DOI=10.1016/0167-4781(92)90164-u;
RA Fujita T., Shirasawa T., Uchida K., Maruyama N.;
RT "Isolation of cDNA clone encoding rat senescence marker protein-30 (SMP30)
RT and its tissue distribution.";
RL Biochim. Biophys. Acta 1132:297-305(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8348951; DOI=10.1016/0014-5793(93)80998-a;
RA Shimokawa N., Yamaguchi M.;
RT "Molecular cloning and sequencing of the cDNA coding for a calcium-binding
RT protein regucalcin from rat liver.";
RL FEBS Lett. 327:251-255(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Misawa H., Yamaguchi M.;
RT "The gene family encoding the calcium-binding protein regucalcin.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115.
RC STRAIN=Sprague-Dawley;
RX PubMed=8979263; DOI=10.1007/bf00229476;
RA Yamaguchi M., Makino R., Shimokawa N.;
RT "The 5' end sequences and exon organization in rat regucalcin gene.";
RL Mol. Cell. Biochem. 165:145-150(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 117-299.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8569761; DOI=10.1007/bf01322338;
RA Shimokawa N., Matsuda Y., Yamaguchi M.;
RT "Genomic cloning and chromosomal assignment of rat regucalcin gene.";
RL Mol. Cell. Biochem. 151:157-163(1995).
RN [7]
RP PROTEIN SEQUENCE OF 113-124, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=16585534; DOI=10.1073/pnas.0511225103;
RA Kondo Y., Inai Y., Sato Y., Handa S., Kubo S., Shimokado K., Goto S.,
RA Nishikimi M., Maruyama N., Ishigami A.;
RT "Senescence marker protein 30 functions as gluconolactonase in L-ascorbic
RT acid biosynthesis, and its knockout mice are prone to scurvy.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5723-5728(2006).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8794449; DOI=10.1016/0047-6374(96)01711-3;
RA Fujita T., Shirasawa T., Uchida K., Maruyama N.;
RT "Gene regulation of senescence marker protein-30 (SMP30): coordinated up-
RT regulation with tissue maturation and gradual down-regulation with aging.";
RL Mech. Ageing Dev. 87:219-229(1996).
RN [9]
RP FUNCTION, AND COFACTOR.
RX PubMed=15251439; DOI=10.1016/j.febslet.2004.06.028;
RA Kondo Y., Ishigami A., Kubo S., Handa S., Gomi K., Hirokawa K.,
RA Kajiyama N., Chiba T., Shimokado K., Maruyama N.;
RT "Senescence marker protein-30 is a unique enzyme that hydrolyzes
RT diisopropyl phosphorofluoridate in the liver.";
RL FEBS Lett. 570:57-62(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Gluconolactonase with low activity towards other sugar
CC lactones, including gulonolactone and galactonolactone. Catalyzes a key
CC step in ascorbic acid (vitamin C) biosynthesis. Can also hydrolyze
CC diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-
CC binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent
CC cellular processes and enzyme activities. {ECO:0000269|PubMed:15251439,
CC ECO:0000269|PubMed:16585534, ECO:0000269|PubMed:8794449}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucono-1,5-lactone + H2O = D-gluconate + H(+);
CC Xref=Rhea:RHEA:10440, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16217, ChEBI:CHEBI:18391; EC=3.1.1.17;
CC Evidence={ECO:0000269|PubMed:16585534};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15251439, ECO:0000269|PubMed:16585534};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15251439, ECO:0000269|PubMed:16585534};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:15251439, ECO:0000269|PubMed:16585534};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15251439, ECO:0000269|PubMed:16585534};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:15251439, ECO:0000269|PubMed:16585534};
CC Note=Binds 1 divalent metal cation per subunit. Most active with Zn(2+)
CC and Mn(2+) ions. The physiological cofactor for gluconolactonase
CC activity is most likely Ca(2+) or Mg(2+). Mg(2+), Mn(2+) and Co(2+) are
CC equally efficient for the hydrolysis of diisopropyl
CC phosphorofluoridate. {ECO:0000269|PubMed:15251439,
CC ECO:0000269|PubMed:16585534};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.4 mM for gluconolactone {ECO:0000269|PubMed:16585534};
CC Vmax=345 umol/min/mg enzyme {ECO:0000269|PubMed:16585534};
CC pH dependence:
CC Optimum pH is 6.4. {ECO:0000269|PubMed:16585534};
CC -!- PATHWAY: Cofactor biosynthesis; L-ascorbate biosynthesis via UDP-alpha-
CC D-glucuronate pathway; L-ascorbate from UDP-alpha-D-glucuronate: step
CC 3/4. {ECO:0000269|PubMed:16585534}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level). Hepatocytes
CC and renal proximal tubular epithelium. {ECO:0000269|PubMed:1420310,
CC ECO:0000269|PubMed:16585534, ECO:0000269|PubMed:8794449}.
CC -!- DEVELOPMENTAL STAGE: In liver, the first peak of expression was found
CC in 5-day-old neonates. Expression increases from day 7 and reaches a
CC plateau at day 10. 3-6.5 moth-old adults express about a third the
CC amount of neonates level. In kidney, expression increases from day 21
CC and reaches a maximal level at day 35, remains high until 3 months of
CC age.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the SMP-30/CGR1 family. {ECO:0000305}.
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DR EMBL; X69021; CAA48786.1; -; mRNA.
DR EMBL; D38467; BAA07490.1; -; mRNA.
DR EMBL; AB037934; BAA90692.1; -; mRNA.
DR EMBL; BC078794; AAH78794.1; -; mRNA.
DR EMBL; D67070; BAA11083.1; -; Genomic_DNA.
DR EMBL; D31662; BAA06507.1; -; Genomic_DNA.
DR PIR; S34588; S34588.
DR RefSeq; NP_113734.1; NM_031546.1.
DR AlphaFoldDB; Q03336; -.
DR SMR; Q03336; -.
DR IntAct; Q03336; 2.
DR STRING; 10116.ENSRNOP00000010984; -.
DR iPTMnet; Q03336; -.
DR PhosphoSitePlus; Q03336; -.
DR PaxDb; Q03336; -.
DR PRIDE; Q03336; -.
DR Ensembl; ENSRNOT00000010984; ENSRNOP00000010984; ENSRNOG00000007949.
DR GeneID; 25106; -.
DR KEGG; rno:25106; -.
DR UCSC; RGD:3560; rat.
DR CTD; 9104; -.
DR RGD; 3560; Rgn.
DR eggNOG; KOG4499; Eukaryota.
DR GeneTree; ENSGT00390000014995; -.
DR HOGENOM; CLU_036110_3_2_1; -.
DR InParanoid; Q03336; -.
DR OMA; AGTMRYD; -.
DR OrthoDB; 1343872at2759; -.
DR PhylomeDB; Q03336; -.
DR TreeFam; TF323663; -.
DR BioCyc; MetaCyc:MON-13233; -.
DR BRENDA; 3.1.8.2; 5301.
DR UniPathway; UPA00991; UER00938.
DR PRO; PR:Q03336; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000007949; Expressed in liver and 16 other tissues.
DR Genevisible; Q03336; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0030234; F:enzyme regulator activity; IEA:InterPro.
DR GO; GO:0004341; F:gluconolactonase activity; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0019853; P:L-ascorbic acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR GO; GO:1903011; P:negative regulation of bone development; IDA:RGD.
DR GO; GO:1903611; P:negative regulation of calcium-dependent ATPase activity; IMP:RGD.
DR GO; GO:0051344; P:negative regulation of cyclic-nucleotide phosphodiesterase activity; IDA:RGD.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IMP:RGD.
DR GO; GO:1903625; P:negative regulation of DNA catabolic process; IDA:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:RGD.
DR GO; GO:1901318; P:negative regulation of flagellated sperm motility; IDA:RGD.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IMP:RGD.
DR GO; GO:1903634; P:negative regulation of leucine-tRNA ligase activity; IDA:RGD.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IMP:RGD.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IMP:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:1902679; P:negative regulation of RNA biosynthetic process; IMP:RGD.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; IDA:UniProtKB.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; IDA:RGD.
DR GO; GO:1903629; P:positive regulation of dUTP diphosphatase activity; IDA:RGD.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IDA:RGD.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; IDA:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:RGD.
DR GO; GO:0010922; P:positive regulation of phosphatase activity; IMP:RGD.
DR GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; IDA:RGD.
DR GO; GO:1901671; P:positive regulation of superoxide dismutase activity; IDA:RGD.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IDA:RGD.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IDA:RGD.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR008367; Regucalcin.
DR InterPro; IPR013658; SGL.
DR InterPro; IPR005511; SMP-30.
DR Pfam; PF08450; SGL; 1.
DR PRINTS; PR01791; REGUCALCIN.
DR PRINTS; PR01790; SMP30FAMILY.
PE 1: Evidence at protein level;
KW Ascorbate biosynthesis; Calcium; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Metal-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..299
FT /note="Regucalcin"
FT /id="PRO_0000173049"
FT ACT_SITE 204
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 18
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 103
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 121
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 204
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 144
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q64374"
FT MOD_RES 244
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q64374"
FT MOD_RES 253
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q64374"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 148
FT /note="D -> N (in Ref. 2; BAA07490 and 6; BAA06507)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 299 AA; 33390 MW; 5D8F2D95FCA4EE35 CRC64;
MSSIKIECVL RENYRCGESP VWEEASKCLL FVDIPSKTVC RWDSISNRVQ RVGVDAPVSS
VALRQSGGYV ATIGTKFCAL NWEDQSVFIL AMVDEDKKNN RFNDGKVDPA GRYFAGTMAE
ETAPAVLERH QGSLYSLFPD HSVKKYFDQV DISNGLDWSL DHKIFYYIDS LSYTVDAFDY
DLPTGQISNR RTVYKMEKDE QIPDGMCIDV EGKLWVACYN GGRVIRLDPE TGKRLQTVKL
PVDKTTSCCF GGKDYSEMYV TCARDGMSAE GLLRQPDAGN IFKITGLGVK GIAPYSYAG
