Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q9BQB4

- SOST_HUMAN

UniProt

Q9BQB4 - SOST_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Sclerostin

Gene

SOST

Organism
Homo sapiens (Human)
Status
Reviewed - 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.1 Publication

GO - Molecular functioni

  1. heparin binding Source: UniProtKB-KW
  2. 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
Complete GO annotation...

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-KW
Complete GO annotation...

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 – 803Combined sources
Beta strandi82 – 876Combined sources
Beta strandi95 – 984Combined sources
Beta strandi100 – 1056Combined sources
Beta strandi139 – 1479Combined sources
Beta strandi155 – 1628Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000014900.
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

        10         20         30         40         50
MQLPLALCLV CLLVHTAFRV VEGQGWQAFK NDATEIIPEL GEYPEPPPEL
60 70 80 90 100
ENNKTMNRAE NGGRPPHHPF ETKDVSEYSC RELHFTRYVT DGPCRSAKPV
110 120 130 140 150
TELVCSGQCG PARLLPNAIG RGKWWRPSGP DFRCIPDRYR AQRVQLLCPG
160 170 180 190 200
GEAPRARKVR LVASCKCKRL TRFHNQSELK DFGTEAARPQ KGRKPRPRAR
210
SAKANQAELE NAY
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.
GeneTreei ENSGT00390000014900.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 121 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