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Q9BQB4 (SOST_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sclerostin
Gene names
Name:SOST
ORF Names:UNQ2976/PRO7455/PRO7476
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length213 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation. Ref.8

Subunit structure

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. Ref.8 Ref.11

Subcellular location

Secretedextracellular spaceextracellular matrix Ref.9.

Tissue specificity

Widely expressed at low levels with highest levels in bone, cartilage, kidney, liver, bone marrow and primary osteoblasts differentiated for 21 days. Detected in the subendothelial layer of the aortic intima (at protein level). Ref.9

Involvement in disease

Sclerosteosis 1 (SOST1) [MIM:269500]: An autosomal recessive sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.13

Van Buchem disease (VBCH) [MIM:239100]: VBCH is an autosomal recessive sclerosing bone dysplasia characterized by endosteal hyperostosis of the mandible, skull, ribs, clavicles, and diaphyses of the long bones. Affected patients present a symmetrically increased thickness of bones, most frequently found as an enlarged jawbone, but also an enlargement of the skull, ribs, diaphysis of long bones, as well as tubular bones of hands and feet. The clinical consequence of increased thickness of the skull include facial nerve palsy causing hearing loss, visual problems, neurological pain, and, very rarely, blindness as a consequence of optic atrophy. Serum alkaline phosphatase levels are elevated.
Note: The disease is caused by mutations affecting the gene represented in this entry. A 52 kb deletion downstream of SOST results in SOST transcription suppression causing van Buchem disease. Ref.7

Craniodiaphyseal dysplasia autosomal dominant (CDD) [MIM:122860]: A severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine faces) and the bone deposition results in progressive stenosis of craniofacial foramina. Respiratory obstruction due to choanal stenosis compromises the clinical outcomes of affected patients.
Note: The disease is caused by mutations affecting the gene represented in this entry. Heterozygous mutations located in the secretion signal of the SOST gene prevent sclerostin secretion and can be responsible for craniodiaphyseal dysplasia. Ref.10

Sequence similarities

Belongs to the sclerostin family.

Contains 1 CTCK (C-terminal cystine knot-like) domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentExtracellular matrix
Secreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
   LigandHeparin-binding
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to parathyroid hormone stimulus

Inferred from direct assay PubMed 17696759. Source: UniProtKB

negative regulation of BMP signaling pathway

Inferred from direct assay PubMed 14633986. Source: MGI

negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification

Inferred from direct assay Ref.8. Source: BHF-UCL

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay Ref.8. Source: BHF-UCL

negative regulation of ossification

Non-traceable author statement Ref.1PubMed 17696759. Source: UniProtKB

negative regulation of protein complex assembly

Inferred from direct assay Ref.8. Source: BHF-UCL

ossification

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 17696759. Source: UniProtKB

response to mechanical stimulus

Inferred from expression pattern PubMed 21723865. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: Ensembl

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionheparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

transcription factor binding

Inferred from direct assay PubMed 17696759. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BQB4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9BQB4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     64-73: RPPHHPFETK → WPGGRPPSRAPLST
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.6
Chain24 – 213190Sclerostin
PRO_0000033177

Regions

Domain82 – 17291CTCK

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1751N-linked (GlcNAc...) Potential
Disulfide bond80 ↔ 134 Ref.12
Disulfide bond94 ↔ 148 Ref.12
Disulfide bond105 ↔ 165 Ref.12
Disulfide bond109 ↔ 167 Ref.12

Natural variations

Alternative sequence64 – 7310RPPHHPFETK → WPGGRPPSRAPLST in isoform 2.
VSP_010189
Natural variant211V → L in CDD; affects protein secretion. Ref.10
VAR_065766
Natural variant211V → M in CDD; de novo mutation; affects protein secretion. Ref.10
VAR_065767
Natural variant1671C → R in SOST1; leads to retention of the mutant protein in the endoplasmic reticulum; leads to a complete loss of function of the protein. Ref.13
VAR_063982

Secondary structure

............. 213
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 30DBD55CE73D5BB2

FASTA21324,031
        10         20         30         40         50         60 
MQLPLALCLV CLLVHTAFRV VEGQGWQAFK NDATEIIPEL GEYPEPPPEL ENNKTMNRAE 

        70         80         90        100        110        120 
NGGRPPHHPF ETKDVSEYSC RELHFTRYVT DGPCRSAKPV TELVCSGQCG PARLLPNAIG 

       130        140        150        160        170        180 
RGKWWRPSGP DFRCIPDRYR AQRVQLLCPG GEAPRARKVR LVASCKCKRL TRFHNQSELK 

       190        200        210 
DFGTEAARPQ KGRKPRPRAR SAKANQAELE NAY 

« Hide

Isoform 2 [UniParc].

Checksum: 652294D9DE5DB402
Show »

FASTA21724,264

References

« Hide 'large scale' references
[1]"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)."
Balemans W., Ebeling M., Patel N., van Hul E., Olson P., Dioszegi M., Lacza C., Wuyts W., van den Ende J., Willems P., Paes-Alves A.F., Hill S., Bueno M., Ramos F.J., Tacconi P., Dikkers F.G., Stratakis C., Lindpaintner K. expand/collapse author list , Vickery B., Foernzler D., Van Hul W.
Hum. Mol. Genet. 10:537-543(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN SOST1.
[2]"Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein."
Brunkow M.E., Gardner J.C., Van Ness J., Paeper B.W., Kovacevich B.R., Proll S., Skonier J.E., Zhao L., Sabo P.J., Fu Y.H., Alisch R.S., Gillett L., Colbert T., Tacconi P., Galas D., Hamersma H., Beighton P., Mulligan J.T.
Am. J. Hum. Genet. 68:577-589(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INVOLVEMENT IN SOST1.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[4]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-38.
[7]"Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease."
Balemans W., Patel N., Ebeling M., Van Hul E., Wuyts W., Lacza C., Dioszegi M., Dikkers F.G., Hildering P., Willems P.J., Verheij J.B., Lindpaintner K., Vickery B., Foernzler D., Van Hul W.
J. Med. Genet. 39:91-97(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN VBCH.
[8]"SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor."
Semenov M., Tamai K., He X.
J. Biol. Chem. 280:26770-26775(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LRP5 AND LRP6.
[9]"Proteomics characterization of extracellular space components in the human aorta."
Didangelos A., Yin X., Mandal K., Baumert M., Jahangiri M., Mayr M.
Mol. Cell. Proteomics 9:2048-2062(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[10]"Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia."
Kim S.J., Bieganski T., Sohn Y.B., Kozlowski K., Semenov M., Okamoto N., Kim C.H., Ko A.R., Ahn G.H., Choi Y.L., Park S.W., Ki C.S., Kim O.H., Nishimura G., Unger S., Superti-Furga A., Jin D.K.
Hum. Genet. 129:497-502(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CDD, VARIANTS CDD MET-21 AND LEU-21, CHARACTERIZATION OF VARIANTS CDD MET-21 AND LEU-21.
[11]"Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function."
Leupin O., Piters E., Halleux C., Hu S., Kramer I., Morvan F., Bouwmeester T., Schirle M., Bueno-Lozano M., Fuentes F.J., Itin P.H., Boudin E., de Freitas F., Jennes K., Brannetti B., Charara N., Ebersbach H., Geisse S. expand/collapse author list , Lu C.X., Bauer A., Van Hul W., Kneissel M.
J. Biol. Chem. 286:19489-19500(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRP4; LRP5 AND LRP6.
[12]"Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation."
Veverka V., Henry A.J., Slocombe P.M., Ventom A., Mulloy B., Muskett F.W., Muzylak M., Greenslade K., Moore A., Zhang L., Gong J., Qian X., Paszty C., Taylor R.J., Robinson M.K., Carr M.D.
J. Biol. Chem. 284:10890-10900(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 25-213, HEPARIN-BINDING, DISULFIDE BONDS.
[13]"First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function."
Piters E., Culha C., Moester M., Van Bezooijen R., Adriaensen D., Mueller T., Weidauer S., Jennes K., de Freitas F., Loewik C., Timmermans J.-P., Van Hul W., Papapoulos S.
Hum. Mutat. 31:E1526-E1543(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SOST1 ARG-167, CHARACTERIZATION OF VARIANT SOST1 ARG-167.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF331844 mRNA. Translation: AAK16158.1.
AF326736 Genomic DNA. Translation: AAK13451.1.
AF326739 mRNA. Translation: AAK13454.1.
AY358203 mRNA. Translation: AAQ88570.1.
AY358627 mRNA. Translation: AAQ88990.1.
AC055813 Genomic DNA. No translation available.
BC101086 mRNA. Translation: AAI01087.1.
BC101087 mRNA. Translation: AAI01088.1.
BC101088 mRNA. Translation: AAI01089.1.
BC101089 mRNA. Translation: AAI01090.1.
RefSeqNP_079513.1. NM_025237.2.
UniGeneHs.349204.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2K8PNMR-A25-213[»]
ProteinModelPortalQ9BQB4.
SMRQ9BQB4. Positions 25-213.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119186. 2 interactions.
DIPDIP-59407N.
IntActQ9BQB4. 98 interactions.
STRING9606.ENSP00000301691.

Polymorphism databases

DMDM20140220.

Proteomic databases

PaxDbQ9BQB4.
PRIDEQ9BQB4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301691; ENSP00000301691; ENSG00000167941. [Q9BQB4-1]
GeneID50964.
KEGGhsa:50964.
UCSCuc002iec.1. human. [Q9BQB4-1]

Organism-specific databases

CTD50964.
GeneCardsGC17M041841.
HGNCHGNC:13771. SOST.
HPACAB025660.
MIM122860. phenotype.
239100. phenotype.
269500. phenotype.
605740. gene.
neXtProtNX_Q9BQB4.
Orphanet1513. Craniodiaphyseal dysplasia.
3416. Hyperostosis corticalis generalisata.
3152. Sclerosteosis.
PharmGKBPA37809.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40285.
HOGENOMHOG000252934.
HOVERGENHBG003729.
InParanoidQ9BQB4.
KOK16834.
OMADVSEYSC.
OrthoDBEOG7CVPZN.
PhylomeDBQ9BQB4.
TreeFamTF353019.

Gene expression databases

BgeeQ9BQB4.
CleanExHS_SOST.
GenevestigatorQ9BQB4.

Family and domain databases

InterProIPR008835. Sclerostin/SOSTDC1.
IPR015665. SOST.
[Graphical view]
PANTHERPTHR14903. PTHR14903. 1 hit.
PTHR14903:SF2. PTHR14903:SF2. 1 hit.
PfamPF05463. Sclerostin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9BQB4.
GeneWikiSclerostin.
SOST.
GenomeRNAi50964.
NextBio53429.
PROQ9BQB4.
SOURCESearch...

Entry information

Entry nameSOST_HUMAN
AccessionPrimary (citable) accession number: Q9BQB4
Secondary accession number(s): Q495N9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: March 19, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM