SOST_MOUSE
ID SOST_MOUSE Reviewed; 211 AA.
AC Q99P68; B2RQA5; Q9D3L7;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Sclerostin {ECO:0000303|PubMed:15778503};
DE Flags: Precursor;
GN Name=Sost {ECO:0000312|MGI:MGI:1921749};
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 [GENOMIC DNA / MRNA].
RC STRAIN=129/SvJ;
RX PubMed=11179006; DOI=10.1086/318811;
RA Brunkow M.E., Gardner J.C., Van Ness J., Paeper B.W., Kovacevich B.R.,
RA Proll S., Skonier J.E., Zhao L., Sabo P.J., Fu Y.H., Alisch R.S.,
RA Gillett L., Colbert T., Tacconi P., Galas D., Hamersma H., Beighton P.,
RA Mulligan J.T.;
RT "Bone dysplasia sclerosteosis results from loss of the SOST gene product, a
RT novel cystine knot-containing protein.";
RL Am. J. Hum. Genet. 68:577-589(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP INTERACTION WITH LRP5 AND LRP6.
RX PubMed=15778503; DOI=10.1074/jbc.m413274200;
RA Li X., Zhang Y., Kang H., Liu W., Liu P., Zhang J., Harris S.E., Wu D.;
RT "Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling.";
RL J. Biol. Chem. 280:19883-19887(2005).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19419300; DOI=10.1359/jbmr.090411;
RA Lin C., Jiang X., Dai Z., Guo X., Weng T., Wang J., Li Y., Feng G., Gao X.,
RA He L.;
RT "Sclerostin mediates bone response to mechanical unloading through
RT antagonizing Wnt/beta-catenin signaling.";
RL J. Bone Miner. Res. 24:1651-1661(2009).
RN [8]
RP STRUCTURE BY NMR OF 59-167, AND DISULFIDE BONDS.
RX PubMed=19166819; DOI=10.1016/j.bbrc.2009.01.062;
RA Weidauer S.E., Schmieder P., Beerbaum M., Schmitz W., Oschkinat H.,
RA Mueller T.D.;
RT "NMR structure of the Wnt modulator protein Sclerostin.";
RL Biochem. Biophys. Res. Commun. 380:160-165(2009).
CC -!- FUNCTION: Negative regulator of bone growth that acts through
CC inhibition of Wnt signaling and bone formation. {ECO:0000250,
CC ECO:0000269|PubMed:19419300}.
CC -!- SUBUNIT: Interacts with LRP4 (via the extracellular domain); the
CC interaction facilitates the inhibition of Wnt signaling. Interacts with
CC LRP5 (via the first two YWTD-EGF repeat domains); the interaction
CC inhibits Wnt-mediated signaling. Interacts with LRP6. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice were resistant to mechanical unloading-
CC induced bone loss. {ECO:0000269|PubMed:19419300}.
CC -!- SIMILARITY: Belongs to the sclerostin family. {ECO:0000305}.
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DR EMBL; AF326737; AAK13452.1; -; Genomic_DNA.
DR EMBL; AF326740; AAK13455.1; -; mRNA.
DR EMBL; AK017295; BAB30678.1; -; mRNA.
DR EMBL; AL591145; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FQ790373; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466558; EDL34073.1; -; Genomic_DNA.
DR EMBL; BC137832; AAI37833.1; -; mRNA.
DR EMBL; BC137833; AAI37834.1; -; mRNA.
DR CCDS; CCDS25481.1; -.
DR RefSeq; NP_077769.4; NM_024449.6.
DR PDB; 2KD3; NMR; -; A=60-167.
DR PDBsum; 2KD3; -.
DR AlphaFoldDB; Q99P68; -.
DR SMR; Q99P68; -.
DR BioGRID; 216800; 2.
DR STRING; 10090.ENSMUSP00000001534; -.
DR GlyGen; Q99P68; 2 sites.
DR PaxDb; Q99P68; -.
DR PRIDE; Q99P68; -.
DR ProteomicsDB; 258711; -.
DR ProteomicsDB; 328983; -.
DR ABCD; Q99P68; 6 sequenced antibodies.
DR Antibodypedia; 29585; 532 antibodies from 33 providers.
DR Ensembl; ENSMUST00000001534; ENSMUSP00000001534; ENSMUSG00000001494.
DR GeneID; 74499; -.
DR KEGG; mmu:74499; -.
DR UCSC; uc011yfn.1; mouse.
DR CTD; 50964; -.
DR MGI; MGI:1921749; Sost.
DR VEuPathDB; HostDB:ENSMUSG00000001494; -.
DR eggNOG; ENOG502QTBG; Eukaryota.
DR GeneTree; ENSGT00390000014900; -.
DR HOGENOM; CLU_087969_1_0_1; -.
DR InParanoid; Q99P68; -.
DR OMA; MQISWAV; -.
DR OrthoDB; 1511387at2759; -.
DR PhylomeDB; Q99P68; -.
DR TreeFam; TF353019; -.
DR Reactome; R-MMU-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR BioGRID-ORCS; 74499; 4 hits in 74 CRISPR screens.
DR EvolutionaryTrace; Q99P68; -.
DR PRO; PR:Q99P68; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q99P68; protein.
DR Bgee; ENSMUSG00000001494; Expressed in aorta tunica media and 69 other tissues.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0036122; F:BMP binding; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; ISO:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:MGI.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:MGI.
DR GO; GO:0001503; P:ossification; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR DisProt; DP02853; -.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR008835; Sclerostin/SOSTDC1.
DR InterPro; IPR015665; SOST.
DR PANTHER; PTHR14903; PTHR14903; 1.
DR PANTHER; PTHR14903:SF4; PTHR14903:SF4; 1.
DR Pfam; PF05463; Sclerostin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Heparin-binding; Reference proteome; Secreted; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..211
FT /note="Sclerostin"
FT /id="PRO_0000033178"
FT DOMAIN 80..170
FT /note="CTCK"
FT REGION 38..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 176..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..190
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 78..132
FT /evidence="ECO:0000269|PubMed:19166819"
FT DISULFID 92..146
FT /evidence="ECO:0000269|PubMed:19166819"
FT DISULFID 103..163
FT /evidence="ECO:0000269|PubMed:19166819"
FT DISULFID 107..165
FT /evidence="ECO:0000269|PubMed:19166819"
FT CONFLICT 72
FT /note="D -> G (in Ref. 1; AAK13455)"
FT TURN 72..76
FT /evidence="ECO:0007829|PDB:2KD3"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:2KD3"
FT STRAND 133..145
FT /evidence="ECO:0007829|PDB:2KD3"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:2KD3"
FT STRAND 153..164
FT /evidence="ECO:0007829|PDB:2KD3"
SQ SEQUENCE 211 AA; 23501 MW; AEB2F972FA708661 CRC64;
MQPSLAPCLI CLLVHAAFCA VEGQGWQAFR NDATEVIPGL GEYPEPPPEN NQTMNRAENG
GRPPHHPYDA KDVSEYSCRE LHYTRFLTDG PCRSAKPVTE LVCSGQCGPA RLLPNAIGRV
KWWRPNGPDF RCIPDRYRAQ RVQLLCPGGA APRSRKVRLV ASCKCKRLTR FHNQSELKDF
GPETARPQKG RKPRPGARGA KANQAELENA Y
