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Protein

Sclerostin

Gene

Sost

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.By similarity

GO - Molecular functioni

  1. heparin binding Source: UniProtKB-KW
  2. transcription factor binding Source: MGI

GO - Biological processi

  1. cellular response to parathyroid hormone stimulus Source: MGI
  2. negative regulation of BMP signaling pathway Source: MGI
  3. negative regulation of canonical Wnt signaling pathway Source: MGI
  4. negative regulation of ossification Source: MGI
  5. negative regulation of protein complex assembly Source: MGI
  6. negative regulation of Wnt signaling pathway Source: MGI
  7. negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification Source: MGI
  8. ossification Source: MGI
  9. positive regulation of transcription, DNA-templated Source: MGI
  10. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

Heparin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Sclerostin
Gene namesi
Name:Sost
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1921749. Sost.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: InterPro
  2. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Disruption phenotypei

Mice were resistant to mechanical unloading-induced bone loss.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 211188SclerostinPRO_0000033178Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi51 – 511N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi78 ↔ 1321 Publication
Disulfide bondi92 ↔ 1461 Publication
Disulfide bondi103 ↔ 1631 Publication
Disulfide bondi107 ↔ 1651 Publication
Glycosylationi173 – 1731N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiQ99P68.

Expressioni

Gene expression databases

CleanExiMM_SOST.
GenevestigatoriQ99P68.

Interactioni

Subunit structurei

Interacts with LRP4 (via the extracellular domain); the interaction facilitates the inhibition of Wnt signaling. Interacts with LRP5 (via the first two YWTD-EGF repeat domains); the interaction inhibits Wnt-mediated signaling. Interacts with LRP6.By similarity

Protein-protein interaction databases

BioGridi216800. 2 interactions.

Structurei

Secondary structure

1
211
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni72 – 765Combined sources
Beta strandi121 – 1233Combined sources
Beta strandi133 – 14513Combined sources
Beta strandi149 – 1513Combined sources
Beta strandi153 – 16412Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KD3NMR-A60-167[»]
ProteinModelPortaliQ99P68.
SMRiQ99P68. Positions 71-167.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99P68.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 17091CTCKAdd
BLAST

Sequence similaritiesi

Belongs to the sclerostin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG40285.
HOGENOMiHOG000252934.
HOVERGENiHBG003729.
InParanoidiQ99P68.
KOiK16834.
PhylomeDBiQ99P68.

Family and domain databases

InterProiIPR008835. Sclerostin/SOSTDC1.
IPR015665. SOST.
[Graphical view]
PANTHERiPTHR14903. PTHR14903. 1 hit.
PTHR14903:SF4. PTHR14903:SF4. 1 hit.
PfamiPF05463. Sclerostin. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99P68-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPSLAPCLI CLLVHAAFCA VEGQGWQAFR NDATEVIPGL GEYPEPPPEN
60 70 80 90 100
NQTMNRAENG GRPPHHPYDA KGVSEYSCRE LHYTRFLTDG PCRSAKPVTE
110 120 130 140 150
LVCSGQCGPA RLLPNAIGRV KWWRPNGPDF RCIPDRYRAQ RVQLLCPGGA
160 170 180 190 200
APRSRKVRLV ASCKCKRLTR FHNQSELKDF GPETARPQKG RKPRPGARGA
210
KANQAELENA Y
Length:211
Mass (Da):23,443
Last modified:June 1, 2001 - v1
Checksum:iAEB094E358E34961
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti72 – 721G → D in BAB30678 (PubMed:16141072).Curated
Sequence conflicti72 – 721G → D in AAK13452 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF326740 mRNA. Translation: AAK13455.1.
AK017295 mRNA. Translation: BAB30678.1.
AF326737 Genomic DNA. Translation: AAK13452.1.
CCDSiCCDS25481.1.
RefSeqiNP_077769.4. NM_024449.6.
UniGeneiMm.265602.

Genome annotation databases

GeneIDi74499.
KEGGimmu:74499.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF326740 mRNA. Translation: AAK13455.1.
AK017295 mRNA. Translation: BAB30678.1.
AF326737 Genomic DNA. Translation: AAK13452.1.
CCDSiCCDS25481.1.
RefSeqiNP_077769.4. NM_024449.6.
UniGeneiMm.265602.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KD3NMR-A60-167[»]
ProteinModelPortaliQ99P68.
SMRiQ99P68. Positions 71-167.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi216800. 2 interactions.

Proteomic databases

PRIDEiQ99P68.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi74499.
KEGGimmu:74499.

Organism-specific databases

CTDi50964.
MGIiMGI:1921749. Sost.

Phylogenomic databases

eggNOGiNOG40285.
HOGENOMiHOG000252934.
HOVERGENiHBG003729.
InParanoidiQ99P68.
KOiK16834.
PhylomeDBiQ99P68.

Miscellaneous databases

EvolutionaryTraceiQ99P68.
NextBioi340962.
PROiQ99P68.
SOURCEiSearch...

Gene expression databases

CleanExiMM_SOST.
GenevestigatoriQ99P68.

Family and domain databases

InterProiIPR008835. Sclerostin/SOSTDC1.
IPR015665. SOST.
[Graphical view]
PANTHERiPTHR14903. PTHR14903. 1 hit.
PTHR14903:SF4. PTHR14903:SF4. 1 hit.
PfamiPF05463. Sclerostin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Strain: 129/SvJ.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Head.
  3. "Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling."
    Li X., Zhang Y., Kang H., Liu W., Liu P., Zhang J., Harris S.E., Wu D.
    J. Biol. Chem. 280:19883-19887(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LRP5 AND LRP6.
  4. "Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling."
    Lin C., Jiang X., Dai Z., Guo X., Weng T., Wang J., Li Y., Feng G., Gao X., He L.
    J. Bone Miner. Res. 24:1651-1661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. Cited for: STRUCTURE BY NMR OF 59-167, DISULFIDE BONDS.

Entry informationi

Entry nameiSOST_MOUSE
AccessioniPrimary (citable) accession number: Q99P68
Secondary accession number(s): Q9D3L7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: February 4, 2015
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.