SOST_RAT
ID SOST_RAT Reviewed; 213 AA.
AC Q99P67;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Sclerostin {ECO:0000250|UniProtKB:Q99P68};
DE Flags: Precursor;
GN Name=Sost {ECO:0000312|RGD:69358};
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].
RC STRAIN=Sprague-Dawley;
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 DOWN-REGULATION BY PTH.
RX PubMed=15946907; DOI=10.1016/j.bone.2005.03.018;
RA Keller H., Kneissel M.;
RT "SOST is a target gene for PTH in bone.";
RL Bone 37:148-158(2005).
CC -!- FUNCTION: Negative regulator of bone growth that acts through
CC inhibition of Wnt signaling and bone formation. {ECO:0000250}.
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 {ECO:0000305}.
CC -!- INDUCTION: Down-regulated by parathyroid hormone (PTH).
CC -!- SIMILARITY: Belongs to the sclerostin family. {ECO:0000305}.
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DR EMBL; AF326741; AAK13456.1; -; mRNA.
DR RefSeq; NP_085073.1; NM_030584.1.
DR AlphaFoldDB; Q99P67; -.
DR SMR; Q99P67; -.
DR STRING; 10116.ENSRNOP00000028238; -.
DR ChEMBL; CHEMBL4523438; -.
DR GlyGen; Q99P67; 2 sites.
DR PaxDb; Q99P67; -.
DR PRIDE; Q99P67; -.
DR Ensembl; ENSRNOT00000099214; ENSRNOP00000081514; ENSRNOG00000071073.
DR GeneID; 80722; -.
DR KEGG; rno:80722; -.
DR UCSC; RGD:69358; rat.
DR CTD; 50964; -.
DR RGD; 69358; Sost.
DR eggNOG; ENOG502QTBG; Eukaryota.
DR GeneTree; ENSGT00390000014900; -.
DR HOGENOM; CLU_087969_1_0_1; -.
DR InParanoid; Q99P67; -.
DR OMA; MQISWAV; -.
DR OrthoDB; 1511387at2759; -.
DR PhylomeDB; Q99P67; -.
DR TreeFam; TF353019; -.
DR Reactome; R-RNO-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR PRO; PR:Q99P67; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000020805; Expressed in thymus and 5 other tissues.
DR Genevisible; Q99P67; RN.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0036122; F:BMP binding; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; ISO:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0001503; P:ossification; IEP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; ISO:RGD.
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 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Heparin-binding; Reference proteome;
KW Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..213
FT /note="Sclerostin"
FT /id="PRO_0000033179"
FT DOMAIN 82..172
FT /note="CTCK"
FT REGION 178..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 80..134
FT /evidence="ECO:0000250"
FT DISULFID 94..148
FT /evidence="ECO:0000250"
FT DISULFID 105..165
FT /evidence="ECO:0000250"
FT DISULFID 109..167
FT /evidence="ECO:0000250"
SQ SEQUENCE 213 AA; 23974 MW; 6C56C878CBCD684B CRC64;
MQLSLAPCLA CLLVHAAFVA VESQGWQAFK NDATEIIPGL REYPEPPQEL ENNQTMNRAE
NGGRPPHHPY DTKDVSEYSC RELHYTRFVT DGPCRSAKPV TELVCSGQCG PARLLPNAIG
RVKWWRPNGP DFRCIPDRYR AQRVQLLCPG GAAPRSRKVR LVASCKCKRL TRFHNQSELK
DFGPETARPQ KGRKPRPRAR GAKANQAELE NAY
