UniProtKB - Q9BQB4 (SOST_HUMAN)
Protein
Sclerostin
Gene
SOST
Organism
Homo sapiens (Human)
Status
Functioni
Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.1 Publication
GO - Molecular functioni
- BMP binding Source: GO_Central
- heparin binding Source: UniProtKB-KW
- transcription factor binding Source: UniProtKB
GO - Biological processi
- cellular response to parathyroid hormone stimulus Source: UniProtKB
- negative regulation of BMP signaling pathway Source: MGI
- negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
- negative regulation of ossification Source: UniProtKB
- negative regulation of protein-containing complex assembly Source: BHF-UCL
- negative regulation of Wnt signaling pathway Source: GO_Central
- ossification Source: GO_Central
- positive regulation of transcription, DNA-templated Source: UniProtKB
- response to mechanical stimulus Source: UniProtKB
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | Heparin-binding |
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q9BQB4 |
Reactomei | R-HSA-201681, TCF dependent signaling in response to WNT R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists |
SIGNORi | Q9BQB4 |
Names & Taxonomyi
Protein namesi | Recommended name: SclerostinBy similarity |
Gene namesi | Name:SOSTImported ORF Names:UNQ2976/PRO7455/PRO7476 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000167941.2 |
HGNCi | HGNC:13771, SOST |
MIMi | 605740, gene |
neXtProti | NX_Q9BQB4 |
Subcellular locationi
Extracellular region or secreted
- extracellular matrix 1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Golgi apparatus
- Golgi apparatus Source: Ensembl
Other locations
- protein-containing complex Source: Ensembl
Keywords - Cellular componenti
Extracellular matrix, SecretedPathology & Biotechi
Involvement in diseasei
Sclerosteosis 1 (SOST1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_063982 | 167 | C → 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 | 1 |
Van Buchem disease (VBCH)1 Publication
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.
Disease descriptionVBCH 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.
Related information in OMIMCraniodiaphyseal dysplasia autosomal dominant (CDD)1 Publication
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.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_065766 | 21 | V → L in CDD; affects protein secretion. 1 Publication | 1 | |
Natural variantiVAR_065767 | 21 | V → M in CDD; de novo mutation; affects protein secretion. 1 PublicationCorresponds to variant dbSNP:rs387907169EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 50964 |
GeneReviewsi | SOST |
MalaCardsi | SOST |
MIMi | 122860, phenotype 239100, phenotype 269500, phenotype |
OpenTargetsi | ENSG00000167941 |
Orphaneti | 1513, Craniodiaphyseal dysplasia 3416, Hyperostosis corticalis generalisata 3152, Sclerosteosis |
PharmGKBi | PA37809 |
Miscellaneous databases
Pharosi | Q9BQB4, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3580487 |
DrugBanki | DB11866, Romosozumab |
Polymorphism and mutation databases
BioMutai | SOST |
DMDMi | 20140220 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | 1 PublicationAdd BLAST | 23 | |
ChainiPRO_0000033177 | 24 – 213 | SclerostinAdd BLAST | 190 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 53 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 80 ↔ 134 | 1 Publication | ||
Disulfide bondi | 94 ↔ 148 | 1 Publication | ||
Disulfide bondi | 105 ↔ 165 | 1 Publication | ||
Disulfide bondi | 109 ↔ 167 | 1 Publication | ||
Glycosylationi | 175 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | Q9BQB4 |
PaxDbi | Q9BQB4 |
PeptideAtlasi | Q9BQB4 |
PRIDEi | Q9BQB4 |
ProteomicsDBi | 78650 [Q9BQB4-1] 78651 [Q9BQB4-2] |
PTM databases
GlyGeni | Q9BQB4, 2 sites |
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
Bgeei | ENSG00000167941, Expressed in metanephros and 60 other tissues |
Genevisiblei | Q9BQB4, HS |
Organism-specific databases
HPAi | ENSG00000167941, Tissue enhanced (kidney, retina) |
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 PublicationsBinary interactionsi
Hide detailsQ9BQB4
With | #Exp. | IntAct |
---|---|---|
LRP4 [O75096] | 5 | EBI-5746563,EBI-310873 |
LRP5 [O75197] | 3 | EBI-5746563,EBI-2466421 |
LRP6 [O75581] | 7 | EBI-5746563,EBI-910915 |
PLEKHF2 [Q9H8W4] | 3 | EBI-5746563,EBI-742388 |
GO - Molecular functioni
- BMP binding Source: GO_Central
- transcription factor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 119186, 134 interactors |
DIPi | DIP-59407N |
ELMi | Q9BQB4 |
IntActi | Q9BQB4, 120 interactors |
STRINGi | 9606.ENSP00000301691 |
Miscellaneous databases
RNActi | Q9BQB4, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9BQB4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9BQB4 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 82 – 172 | CTCKAdd BLAST | 91 |
Sequence similaritiesi
Belongs to the sclerostin family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QTBG, Eukaryota |
GeneTreei | ENSGT00390000014900 |
HOGENOMi | CLU_087969_1_0_1 |
InParanoidi | Q9BQB4 |
OMAi | PNSIGRG |
OrthoDBi | 1008844at2759 |
PhylomeDBi | Q9BQB4 |
TreeFami | TF353019 |
Family and domain databases
DisProti | DP00926 |
Gene3Di | 2.10.90.10, 1 hit |
IDEALi | IID00584 |
InterProi | View protein in InterPro IPR006207, Cys_knot_C IPR029034, Cystine-knot_cytokine IPR008835, Sclerostin/SOSTDC1 IPR015665, SOST |
PANTHERi | PTHR14903, PTHR14903, 1 hit PTHR14903:SF4, PTHR14903:SF4, 1 hit |
Pfami | View protein in Pfam PF05463, Sclerostin, 1 hit |
SMARTi | View protein in SMART SM00041, CT, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q9BQB4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_065766 | 21 | V → L in CDD; affects protein secretion. 1 Publication | 1 | |
Natural variantiVAR_065767 | 21 | V → M in CDD; de novo mutation; affects protein secretion. 1 PublicationCorresponds to variant dbSNP:rs387907169EnsemblClinVar. | 1 | |
Natural variantiVAR_063982 | 167 | C → 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 | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010189 | 64 – 73 | RPPHHPFETK → WPGGRPPSRAPLST in isoform 2. 1 Publication | 10 |
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] |
Genome annotation databases
Ensembli | ENST00000301691; ENSP00000301691; ENSG00000167941 [Q9BQB4-1] |
GeneIDi | 50964 |
KEGGi | hsa:50964 |
UCSCi | uc002iec.1, human [Q9BQB4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2K8P | NMR | - | A | 25-213 | [»] | |
3SOV | X-ray | 1.27 | Z | 115-121 | [»] | |
SMRi | Q9BQB4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 119186, 134 interactors |
DIPi | DIP-59407N |
ELMi | Q9BQB4 |
IntActi | Q9BQB4, 120 interactors |
STRINGi | 9606.ENSP00000301691 |
Chemistry databases
ChEMBLi | CHEMBL3580487 |
DrugBanki | DB11866, Romosozumab |
PTM databases
GlyGeni | Q9BQB4, 2 sites |
Polymorphism and mutation databases
BioMutai | SOST |
DMDMi | 20140220 |
Proteomic databases
MassIVEi | Q9BQB4 |
PaxDbi | Q9BQB4 |
PeptideAtlasi | Q9BQB4 |
PRIDEi | Q9BQB4 |
ProteomicsDBi | 78650 [Q9BQB4-1] 78651 [Q9BQB4-2] |
Protocols and materials databases
ABCDi | Q9BQB4, 12 sequenced antibodies |
Antibodypediai | 29585, 551 antibodies |
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 |
DisGeNETi | 50964 |
EuPathDBi | HostDB:ENSG00000167941.2 |
GeneCardsi | SOST |
GeneReviewsi | SOST |
HGNCi | HGNC:13771, SOST |
HPAi | ENSG00000167941, Tissue enhanced (kidney, retina) |
MalaCardsi | SOST |
MIMi | 122860, phenotype 239100, phenotype 269500, phenotype 605740, gene |
neXtProti | NX_Q9BQB4 |
OpenTargetsi | ENSG00000167941 |
Orphaneti | 1513, Craniodiaphyseal dysplasia 3416, Hyperostosis corticalis generalisata 3152, Sclerosteosis |
PharmGKBi | PA37809 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QTBG, Eukaryota |
GeneTreei | ENSGT00390000014900 |
HOGENOMi | CLU_087969_1_0_1 |
InParanoidi | Q9BQB4 |
OMAi | PNSIGRG |
OrthoDBi | 1008844at2759 |
PhylomeDBi | Q9BQB4 |
TreeFami | TF353019 |
Enzyme and pathway databases
PathwayCommonsi | Q9BQB4 |
Reactomei | R-HSA-201681, TCF dependent signaling in response to WNT R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists |
SIGNORi | Q9BQB4 |
Miscellaneous databases
BioGRID-ORCSi | 50964, 4 hits in 837 CRISPR screens |
EvolutionaryTracei | Q9BQB4 |
GeneWikii | Sclerostin SOST |
GenomeRNAii | 50964 |
Pharosi | Q9BQB4, Tbio |
PROi | PR:Q9BQB4 |
RNActi | Q9BQB4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167941, Expressed in metanephros and 60 other tissues |
Genevisiblei | Q9BQB4, HS |
Family and domain databases
DisProti | DP00926 |
Gene3Di | 2.10.90.10, 1 hit |
IDEALi | IID00584 |
InterProi | View protein in InterPro IPR006207, Cys_knot_C IPR029034, Cystine-knot_cytokine IPR008835, Sclerostin/SOSTDC1 IPR015665, SOST |
PANTHERi | PTHR14903, PTHR14903, 1 hit PTHR14903:SF4, PTHR14903:SF4, 1 hit |
Pfami | View protein in Pfam PF05463, Sclerostin, 1 hit |
SMARTi | View protein in SMART SM00041, CT, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SOST_HUMAN | |
Accessioni | Q9BQB4Primary (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: | December 2, 2020 | |
This is version 164 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations