OSTN_HUMAN
ID OSTN_HUMAN Reviewed; 133 AA.
AC P61366; A1A4U3;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Osteocrin {ECO:0000303|PubMed:14523025};
DE AltName: Full=Musclin {ECO:0000303|PubMed:15044443};
DE Contains:
DE RecName: Full=Processed Osteocrin {ECO:0000250|UniProtKB:P61364};
DE Flags: Precursor;
GN Name=OSTN {ECO:0000312|HGNC:HGNC:29961};
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow;
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].
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 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 TISSUE SPECIFICITY.
RX PubMed=15923362; DOI=10.1369/jhc.4c6561.2005;
RA Bord S., Ireland D.C., Moffatt P., Thomas G.P., Compston J.E.;
RT "Characterization of osteocrin expression in human bone.";
RL J. Histochem. Cytochem. 53:1181-1187(2005).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
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 regulator of dendritic growth in the
CC developing cerebral cortex in response to sensory experience
CC (PubMed:27830782). Induced in the brain following membrane
CC depolarization and inhibits dendritic branching in neurons of the
CC developing cortex (PubMed:27830782). Probably acts by binding to
CC natriuretic peptide receptor NPR3/NPR-C, thereby preventing binding
CC between NPR3/NPR-C and natriuretic peptides, leading to increase cGMP
CC production (By similarity). {ECO:0000250|UniProtKB:P61364,
CC ECO:0000269|PubMed:27830782}.
CC -!- SUBUNIT: Interacts with NPR3. {ECO:0000250|UniProtKB:P61364}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14523025}.
CC -!- TISSUE SPECIFICITY: Enriched in neocortical regions of the developing
CC cerebral cortex (PubMed:27830782). Not expressed in other compartments
CC of the neocortical wall or in brain regions such as the hippocampus,
CC striatum, mediodorsal nucleus of the thalamus and cerebellum
CC (PubMed:27830782). Also expressed in bone (PubMed:14523025). In
CC developing neonatal rib bone, present at high level in osteoblasts on
CC bone-forming surfaces, in newly incorporated osteocytes and in some
CC late hypertrophic chondrocytes (at protein level) (PubMed:15923362). In
CC adult bone, localizes specifically to osteoblasts and young osteocytes
CC at bone-forming sites (at protein level) (PubMed:15923362).
CC {ECO:0000269|PubMed:14523025, ECO:0000269|PubMed:15923362,
CC ECO:0000269|PubMed:27830782}.
CC -!- DEVELOPMENTAL STAGE: Expression in the developing cerebral cortex
CC increases during the course of fetal development and peaks around the
CC late-mid fetal stage, concurrent with the onset of synaptogenesis in
CC the cortical plate (PubMed:27830782). {ECO:0000269|PubMed:27830782}.
CC -!- INDUCTION: Expression is induced in the developing cerebral cortex in
CC response to neuronal activity in neurons: expression is driven by the
CC presence of a enhancer sequence only present in primates that binds the
CC MEF2 transcription factors (PubMed:27830782).
CC {ECO:0000269|PubMed:27830782}.
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, leading to restrict dendritic growth
CC in the developing cortex (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; AY398681; AAQ94966.1; -; mRNA.
DR EMBL; AY573933; AAS87599.1; -; mRNA.
DR EMBL; CH471052; EAW78095.1; -; Genomic_DNA.
DR EMBL; BC128106; AAI28107.1; -; mRNA.
DR EMBL; BC128107; AAI28108.1; -; mRNA.
DR CCDS; CCDS3299.1; -.
DR RefSeq; NP_937827.1; NM_198184.2.
DR RefSeq; XP_016861792.1; XM_017006303.1.
DR AlphaFoldDB; P61366; -.
DR BioGRID; 131332; 8.
DR STRING; 9606.ENSP00000342356; -.
DR iPTMnet; P61366; -.
DR PhosphoSitePlus; P61366; -.
DR BioMuta; OSTN; -.
DR DMDM; 47117104; -.
DR MassIVE; P61366; -.
DR PaxDb; P61366; -.
DR PRIDE; P61366; -.
DR Antibodypedia; 56755; 109 antibodies from 14 providers.
DR DNASU; 344901; -.
DR Ensembl; ENST00000682035.1; ENSP00000508312.1; ENSG00000188729.7.
DR GeneID; 344901; -.
DR KEGG; hsa:344901; -.
DR MANE-Select; ENST00000682035.1; ENSP00000508312.1; NM_198184.2; NP_937827.1.
DR UCSC; uc011bsn.2; human.
DR CTD; 344901; -.
DR DisGeNET; 344901; -.
DR GeneCards; OSTN; -.
DR HGNC; HGNC:29961; OSTN.
DR HPA; ENSG00000188729; Low tissue specificity.
DR MIM; 610280; gene.
DR neXtProt; NX_P61366; -.
DR OpenTargets; ENSG00000188729; -.
DR PharmGKB; PA134912892; -.
DR VEuPathDB; HostDB:ENSG00000188729; -.
DR eggNOG; ENOG502S2R3; Eukaryota.
DR GeneTree; ENSGT00390000001750; -.
DR HOGENOM; CLU_155967_0_0_1; -.
DR InParanoid; P61366; -.
DR OMA; AIFLMQW; -.
DR OrthoDB; 1512795at2759; -.
DR PhylomeDB; P61366; -.
DR TreeFam; TF333399; -.
DR PathwayCommons; P61366; -.
DR BioGRID-ORCS; 344901; 5 hits in 1056 CRISPR screens.
DR ChiTaRS; OSTN; human.
DR GenomeRNAi; 344901; -.
DR Pharos; P61366; Tbio.
DR PRO; PR:P61366; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P61366; protein.
DR Bgee; ENSG00000188729; Expressed in cortical plate and 88 other tissues.
DR ExpressionAtlas; P61366; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0003416; P:endochondral bone growth; IEA:Ensembl.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:1903860; P:negative regulation of dendrite extension; IMP:UniProtKB.
DR GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
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; Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..133
FT /note="Osteocrin"
FT /evidence="ECO:0000250|UniProtKB:P61364"
FT /id="PRO_0000439029"
FT PEPTIDE 83..132
FT /note="Processed Osteocrin"
FT /evidence="ECO:0000250|UniProtKB:P61364"
FT /id="PRO_0000021966"
FT MOD_RES 132
FT /note="Arginine amide"
FT /evidence="ECO:0000255"
SQ SEQUENCE 133 AA; 14722 MW; 00898A0B6BABFC5C CRC64;
MLDWRLASAH FILAVTLTLW SSGKVLSVDV TTTEAFDSGV IDVQSTPTVR EEKSATDLTA
KLLLLDELVS LENDVIETKK KRSFSGFGSP LDRLSAGSVD HKGKQRKVVD HPKRRFGIPM
DRIGRNRLSN SRG
