OSTN_MOUSE
ID OSTN_MOUSE Reviewed; 130 AA.
AC P61364; Q149W1;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Osteocrin {ECO:0000303|PubMed:14523025};
DE AltName: Full=Musclin {ECO:0000303|PubMed:15044443};
DE Contains:
DE RecName: Full=Processed Osteocrin {ECO:0000305|PubMed:14523025};
DE Flags: Precursor;
GN Name=Ostn {ECO:0000312|MGI:MGI:2677164};
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 76-LYS--ARG-79.
RC STRAIN=CD-1; TISSUE=Calvaria;
RX PubMed=14523025; DOI=10.1074/jbc.m307310200;
RA Thomas G., Moffatt P., Salois P., Gaumond M.-H., Gingras R., Godin E.,
RA Miao D., Goltzman D., Lanctot C.;
RT "Osteocrin, a novel bone-specific secreted protein that modulates the
RT osteoblast phenotype.";
RL J. Biol. Chem. 278:50563-50571(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND MUTAGENESIS OF
RP 76-LYS--ARG-79.
RC STRAIN=C57BL/6J; TISSUE=Skeletal muscle;
RX PubMed=15044443; DOI=10.1074/jbc.c400066200;
RA Nishizawa H., Matsuda M., Yamada Y., Kawai K., Suzuki E., Makishima M.,
RA Kitamura T., Shimomura I.;
RT "Musclin, a novel skeletal muscle-derived secretory factor.";
RL J. Biol. Chem. 279:19391-19395(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [4]
RP FUNCTION, AND INTERACTION WITH NPR3.
RX PubMed=17951249; DOI=10.1074/jbc.m708596200;
RA Moffatt P., Thomas G., Sellin K., Bessette M.C., Lafreniere F.,
RA Akhouayri O., St-Arnaud R., Lanctot C.;
RT "Osteocrin is a specific ligand of the natriuretic Peptide clearance
RT receptor that modulates bone growth.";
RL J. Biol. Chem. 282:36454-36462(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=26668395; DOI=10.1073/pnas.1514250112;
RA Subbotina E., Sierra A., Zhu Z., Gao Z., Koganti S.R., Reyes S.,
RA Stepniak E., Walsh S.A., Acevedo M.R., Perez-Terzic C.M.,
RA Hodgson-Zingman D.M., Zingman L.V.;
RT "Musclin is an activity-stimulated myokine that enhances physical
RT endurance.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:16042-16047(2015).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=27830782; DOI=10.1038/nature20111;
RA Ataman B., Boulting G.L., Harmin D.A., Yang M.G., Baker-Salisbury M.,
RA Yap E.L., Malik A.N., Mei K., Rubin A.A., Spiegel I., Durresi E.,
RA Sharma N., Hu L.S., Pletikos M., Griffith E.C., Partlow J.N., Stevens C.R.,
RA Adli M., Chahrour M., Sestan N., Walsh C.A., Berezovskii V.K.,
RA Livingstone M.S., Greenberg M.E.;
RT "Evolution of Osteocrin as an activity-regulated factor in the primate
RT brain.";
RL Nature 539:242-247(2016).
CC -!- FUNCTION: Hormone that acts as a ligand for natriuretic peptide
CC receptor NPR3/NPR-C and promotes bone growth and physical endurance in
CC muscle. Acts as a regulator of osteoblast differentiation and bone
CC growth by binding to natriuretic peptide receptor NPR3/NPR-C, thereby
CC preventing binding between NPR3/NPR-C and natriuretic peptides, leading
CC to increase cGMP production (PubMed:14523025, PubMed:17951249).
CC Required to enhance physical endurance: induced following physical
CC exercise in muscle and promotes cGMP production, probably by
CC interacting with NPR3/NPR-C (PubMed:26668395). May act as an autocrine
CC and paracrine factor linked to glucose metabolism in skeletal muscle
CC (PubMed:15044443). {ECO:0000269|PubMed:14523025,
CC ECO:0000269|PubMed:15044443, ECO:0000269|PubMed:17951249,
CC ECO:0000269|PubMed:26668395}.
CC -!- SUBUNIT: Interacts with NPR3. {ECO:0000269|PubMed:17951249}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14523025,
CC ECO:0000269|PubMed:15044443, ECO:0000269|PubMed:26668395}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle and to a much lesser
CC extent in bone, brown adipose tissue, spleen and testis
CC (PubMed:14523025, PubMed:15044443, PubMed:26668395). Not expressed in
CC neurons (PubMed:27830782). {ECO:0000269|PubMed:14523025,
CC ECO:0000269|PubMed:15044443, ECO:0000269|PubMed:26668395,
CC ECO:0000269|PubMed:27830782}.
CC -!- DEVELOPMENTAL STAGE: Expressed during matrix production and maturation.
CC Also expressed during myocyte differentiation.
CC {ECO:0000269|PubMed:14523025, ECO:0000269|PubMed:15044443}.
CC -!- INDUCTION: Is regulated by nutritional changes (PubMed:15044443). Is
CC up-regulated dose-dependently by insulin (PubMed:15044443). Is down-
CC regulated dose-dependently by forskolin (PubMed:15044443). Induced in
CC muscle following physical exercise (PubMed:26668395).
CC {ECO:0000269|PubMed:15044443, ECO:0000269|PubMed:26668395}.
CC -!- DISRUPTION PHENOTYPE: Mice grow normally and do not display any visible
CC phenotype but show reduced physical endurance (PubMed:26668395). Mice
CC do not show skeletal deformities, differences in bone density, growth
CC abnormalities, blood pressure nor body composition changes
CC (PubMed:26668395). {ECO:0000269|PubMed:26668395}.
CC -!- SIMILARITY: Belongs to the Osteocrin family. {ECO:0000305}.
CC -!- CAUTION: This protein-coding gene has been repurposed in primates, with
CC the presence of a new enhancer sequence that drives expression in brain
CC in response to sensory experience (PubMed:27830782).
CC {ECO:0000269|PubMed:27830782}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Something else - Issue 189
CC of March 2017;
CC URL="https://web.expasy.org/spotlight/back_issues/189/";
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DR EMBL; AY395730; AAQ84523.1; -; mRNA.
DR EMBL; AY573932; AAS87598.1; -; mRNA.
DR EMBL; BC117063; AAI17064.1; -; mRNA.
DR EMBL; BC117089; AAI17090.1; -; mRNA.
DR CCDS; CCDS28090.1; -.
DR RefSeq; NP_932780.1; NM_198112.2.
DR AlphaFoldDB; P61364; -.
DR STRING; 10090.ENSMUSP00000067539; -.
DR PhosphoSitePlus; P61364; -.
DR PaxDb; P61364; -.
DR PRIDE; P61364; -.
DR Antibodypedia; 56755; 109 antibodies from 14 providers.
DR Ensembl; ENSMUST00000066852; ENSMUSP00000067539; ENSMUSG00000052276.
DR GeneID; 239790; -.
DR KEGG; mmu:239790; -.
DR UCSC; uc007yvl.1; mouse.
DR CTD; 344901; -.
DR MGI; MGI:2677164; Ostn.
DR VEuPathDB; HostDB:ENSMUSG00000052276; -.
DR eggNOG; ENOG502S2R3; Eukaryota.
DR GeneTree; ENSGT00390000001750; -.
DR HOGENOM; CLU_155967_0_0_1; -.
DR InParanoid; P61364; -.
DR OMA; AIFLMQW; -.
DR OrthoDB; 1512795at2759; -.
DR PhylomeDB; P61364; -.
DR TreeFam; TF333399; -.
DR BioGRID-ORCS; 239790; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Ostn; mouse.
DR PRO; PR:P61364; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P61364; protein.
DR Bgee; ENSMUSG00000052276; Expressed in hindlimb stylopod muscle and 21 other tissues.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; IDA:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0003416; P:endochondral bone growth; IDA:MGI.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IDA:MGI.
DR GO; GO:1903860; P:negative regulation of dendrite extension; ISO:MGI.
DR GO; GO:0046325; P:negative regulation of glucose import; IDA:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:MGI.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0030500; P:regulation of bone mineralization; IC:MGI.
DR InterPro; IPR021088; Osteocrin.
DR PANTHER; PTHR35353; PTHR35353; 1.
DR Pfam; PF11037; Musclin; 1.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Developmental protein;
KW Differentiation; Hormone; Osteogenesis; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..130
FT /note="Osteocrin"
FT /evidence="ECO:0000305|PubMed:14523025"
FT /id="PRO_0000439030"
FT PEPTIDE 80..129
FT /note="Processed Osteocrin"
FT /evidence="ECO:0000305|PubMed:14523025,
FT ECO:0000305|PubMed:15044443"
FT /id="PRO_0000021968"
FT MOD_RES 129
FT /note="Arginine amide"
FT /evidence="ECO:0000255"
FT MUTAGEN 76..79
FT /note="KKKR->A: Abolishes processing of the protein."
FT /evidence="ECO:0000269|PubMed:14523025,
FT ECO:0000269|PubMed:15044443"
FT MUTAGEN 76..79
FT /note="KKKR->AS: Abolishes processing of the protein."
FT /evidence="ECO:0000269|PubMed:14523025,
FT ECO:0000269|PubMed:15044443"
SQ SEQUENCE 130 AA; 14438 MW; C87AFF0EB5BF724B CRC64;
MLDWRLASTH FILAMIVMLW GSGKAFSVDL ASQEFGTASL QSPPTAREEK SATELSAKLL
RLDDLVSLEN DVFETKKKRS FSGFGSPLDR LSAGSVEHRG KQRKAVDHSK KRFGIPMDRI
GRNRLSSSRG
