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Q9BQB4

- SOST_HUMAN

UniProt

Q9BQB4 - SOST_HUMAN

Protein

Sclerostin

Gene

SOST

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    Functioni

    Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.1 Publication

    GO - Molecular functioni

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

    GO - Biological processi

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

    Keywords - Biological processi

    Wnt signaling pathway

    Keywords - Ligandi

    Heparin-binding

    Enzyme and pathway databases

    ReactomeiREACT_200643. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
    REACT_200777. TCF dependent signaling in response to WNT.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sclerostin
    Gene namesi
    Name:SOST
    ORF Names:UNQ2976/PRO7455/PRO7476
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:13771. SOST.

    Subcellular locationi

    Secretedextracellular spaceextracellular matrix 1 Publication

    GO - Cellular componenti

    1. extracellular space Source: Ensembl
    2. Golgi apparatus Source: Ensembl
    3. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti167 – 1671C → R in SOST1; leads to retention of the mutant protein in the endoplasmic reticulum; leads to a complete loss of function of the protein. 1 Publication
    VAR_063982
    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.1 Publication
    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.
    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.1 Publication
    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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti21 – 211V → L in CDD; affects protein secretion. 1 Publication
    VAR_065766
    Natural varianti21 – 211V → M in CDD; de novo mutation; affects protein secretion. 1 Publication
    VAR_065767

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi122860. phenotype.
    239100. phenotype.
    269500. phenotype.
    Orphaneti1513. Craniodiaphyseal dysplasia.
    3416. Hyperostosis corticalis generalisata.
    3152. Sclerosteosis.
    PharmGKBiPA37809.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 23231 PublicationAdd
    BLAST
    Chaini24 – 213190SclerostinPRO_0000033177Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi80 ↔ 1341 Publication
    Disulfide bondi94 ↔ 1481 Publication
    Disulfide bondi105 ↔ 1651 Publication
    Disulfide bondi109 ↔ 1671 Publication
    Glycosylationi175 – 1751N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ9BQB4.
    PRIDEiQ9BQB4.

    Expressioni

    Tissue specificityi

    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).1 Publication

    Gene expression databases

    BgeeiQ9BQB4.
    CleanExiHS_SOST.
    GenevestigatoriQ9BQB4.

    Organism-specific databases

    HPAiCAB025660.

    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 LRP6.2 Publications

    Protein-protein interaction databases

    BioGridi119186. 2 interactions.
    DIPiDIP-59407N.
    IntActiQ9BQB4. 98 interactions.
    STRINGi9606.ENSP00000301691.

    Structurei

    Secondary structure

    1
    213
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi78 – 803
    Beta strandi82 – 876
    Beta strandi95 – 984
    Beta strandi100 – 1056
    Beta strandi139 – 1479
    Beta strandi155 – 1628

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2K8PNMR-A25-213[»]
    ProteinModelPortaliQ9BQB4.
    SMRiQ9BQB4. Positions 25-213.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9BQB4.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini82 – 17291CTCKAdd
    BLAST

    Sequence similaritiesi

    Belongs to the sclerostin family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG40285.
    HOGENOMiHOG000252934.
    HOVERGENiHBG003729.
    InParanoidiQ9BQB4.
    KOiK16834.
    OMAiENNKTMN.
    OrthoDBiEOG7CVPZN.
    PhylomeDBiQ9BQB4.
    TreeFamiTF353019.

    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]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9BQB4-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MQLPLALCLV CLLVHTAFRV VEGQGWQAFK NDATEIIPEL GEYPEPPPEL    50
    ENNKTMNRAE NGGRPPHHPF ETKDVSEYSC RELHFTRYVT DGPCRSAKPV 100
    TELVCSGQCG PARLLPNAIG RGKWWRPSGP DFRCIPDRYR AQRVQLLCPG 150
    GEAPRARKVR LVASCKCKRL TRFHNQSELK DFGTEAARPQ KGRKPRPRAR 200
    SAKANQAELE NAY 213
    Length:213
    Mass (Da):24,031
    Last modified:June 1, 2001 - v1
    Checksum:i30DBD55CE73D5BB2
    GO
    Isoform 2 (identifier: Q9BQB4-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         64-73: RPPHHPFETK → WPGGRPPSRAPLST

    Note: No experimental confirmation available.

    Show »
    Length:217
    Mass (Da):24,264
    Checksum:i652294D9DE5DB402
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti21 – 211V → L in CDD; affects protein secretion. 1 Publication
    VAR_065766
    Natural varianti21 – 211V → M in CDD; de novo mutation; affects protein secretion. 1 Publication
    VAR_065767
    Natural varianti167 – 1671C → R in SOST1; leads to retention of the mutant protein in the endoplasmic reticulum; leads to a complete loss of function of the protein. 1 Publication
    VAR_063982

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei64 – 7310RPPHHPFETK → WPGGRPPSRAPLST in isoform 2. 1 PublicationVSP_010189

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS11468.1. [Q9BQB4-1]
    RefSeqiNP_079513.1. NM_025237.2. [Q9BQB4-1]
    UniGeneiHs.349204.

    Genome annotation databases

    EnsembliENST00000301691; ENSP00000301691; ENSG00000167941. [Q9BQB4-1]
    GeneIDi50964.
    KEGGihsa:50964.
    UCSCiuc002iec.1. human. [Q9BQB4-1]

    Polymorphism databases

    DMDMi20140220.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS11468.1. [Q9BQB4-1 ]
    RefSeqi NP_079513.1. NM_025237.2. [Q9BQB4-1 ]
    UniGenei Hs.349204.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2K8P NMR - A 25-213 [» ]
    ProteinModelPortali Q9BQB4.
    SMRi Q9BQB4. Positions 25-213.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119186. 2 interactions.
    DIPi DIP-59407N.
    IntActi Q9BQB4. 98 interactions.
    STRINGi 9606.ENSP00000301691.

    Polymorphism databases

    DMDMi 20140220.

    Proteomic databases

    PaxDbi Q9BQB4.
    PRIDEi Q9BQB4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000301691 ; ENSP00000301691 ; ENSG00000167941 . [Q9BQB4-1 ]
    GeneIDi 50964.
    KEGGi hsa:50964.
    UCSCi uc002iec.1. human. [Q9BQB4-1 ]

    Organism-specific databases

    CTDi 50964.
    GeneCardsi GC17M041841.
    GeneReviewsi SOST.
    HGNCi HGNC:13771. SOST.
    HPAi CAB025660.
    MIMi 122860. phenotype.
    239100. phenotype.
    269500. phenotype.
    605740. gene.
    neXtProti NX_Q9BQB4.
    Orphaneti 1513. Craniodiaphyseal dysplasia.
    3416. Hyperostosis corticalis generalisata.
    3152. Sclerosteosis.
    PharmGKBi PA37809.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG40285.
    HOGENOMi HOG000252934.
    HOVERGENi HBG003729.
    InParanoidi Q9BQB4.
    KOi K16834.
    OMAi ENNKTMN.
    OrthoDBi EOG7CVPZN.
    PhylomeDBi Q9BQB4.
    TreeFami TF353019.

    Enzyme and pathway databases

    Reactomei REACT_200643. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
    REACT_200777. TCF dependent signaling in response to WNT.

    Miscellaneous databases

    EvolutionaryTracei Q9BQB4.
    GeneWikii Sclerostin.
    SOST.
    GenomeRNAii 50964.
    NextBioi 53429.
    PROi Q9BQB4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9BQB4.
    CleanExi HS_SOST.
    Genevestigatori Q9BQB4.

    Family and domain databases

    InterProi IPR008835. Sclerostin/SOSTDC1.
    IPR015665. SOST.
    [Graphical view ]
    PANTHERi PTHR14903. PTHR14903. 1 hit.
    PTHR14903:SF4. PTHR14903:SF4. 1 hit.
    Pfami PF05463. Sclerostin. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN SOST1.
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INVOLVEMENT IN SOST1.
    3. 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.
      , 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. 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. 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. Cited for: VARIANT SOST1 ARG-167, CHARACTERIZATION OF VARIANT SOST1 ARG-167.

    Entry informationi

    Entry nameiSOST_HUMAN
    AccessioniPrimary (citable) accession number: Q9BQB4
    Secondary accession number(s): Q495N9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 5, 2002
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3