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Protein

Sclerostin

Gene

SOST

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • heparin binding Source: UniProtKB-KW
  • transcription factor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-3772470 Negative regulation of TCF-dependent signaling by WNT ligand antagonists
SIGNORiQ9BQB4

Names & Taxonomyi

Protein namesi
Recommended name:
Sclerostin
Gene namesi
Name:SOST
ORF Names:UNQ2976/PRO7455/PRO7476
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000167941.2
HGNCiHGNC:13771 SOST
MIMi605740 gene
neXtProtiNX_Q9BQB4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & 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.
See also OMIM:269500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063982167C → 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 Publication1
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.
See also OMIM:239100
Craniodiaphyseal 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.
See also OMIM:122860
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06576621V → L in CDD; affects protein secretion. 1 Publication1
Natural variantiVAR_06576721V → M in CDD; de novo mutation; affects protein secretion. 1 PublicationCorresponds to variant dbSNP:rs387907169EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi50964
GeneReviewsiSOST
MalaCardsiSOST
MIMi122860 phenotype
239100 phenotype
269500 phenotype
OpenTargetsiENSG00000167941
Orphaneti1513 Craniodiaphyseal dysplasia
3416 Hyperostosis corticalis generalisata
3152 Sclerosteosis
PharmGKBiPA37809

Chemistry databases

ChEMBLiCHEMBL3580487

Polymorphism and mutation databases

BioMutaiSOST
DMDMi20140220

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000003317724 – 213SclerostinAdd BLAST190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi53N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi80 ↔ 1341 Publication
Disulfide bondi94 ↔ 1481 Publication
Disulfide bondi105 ↔ 1651 Publication
Disulfide bondi109 ↔ 1671 Publication
Glycosylationi175N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9BQB4
PeptideAtlasiQ9BQB4
PRIDEiQ9BQB4
ProteomicsDBi78650
78651 [Q9BQB4-2]

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

BgeeiENSG00000167941 Expressed in 46 organ(s), highest expression level in metanephros
CleanExiHS_SOST
GenevisibleiQ9BQB4 HS

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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119186, 25 interactors
DIPiDIP-59407N
ELMiQ9BQB4
IntActiQ9BQB4, 101 interactors
STRINGi9606.ENSP00000301691

Structurei

Secondary structure

1213
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00926
ProteinModelPortaliQ9BQB4
SMRiQ9BQB4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BQB4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 172CTCKAdd BLAST91

Sequence similaritiesi

Belongs to the sclerostin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVV4 Eukaryota
ENOG4111KFN LUCA
GeneTreeiENSGT00390000014900
HOGENOMiHOG000252934
HOVERGENiHBG003729
InParanoidiQ9BQB4
KOiK16834
OMAiDVSEYSC
OrthoDBiEOG091G13DX
PhylomeDBiQ9BQB4
TreeFamiTF353019

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR006207 Cys_knot_C
IPR029034 Cystine-knot_cytokine
IPR008835 Sclerostin/SOSTDC1
IPR015665 SOST
PANTHERiPTHR14903 PTHR14903, 1 hit
PTHR14903:SF4 PTHR14903:SF4, 1 hit
PfamiView protein in Pfam
PF05463 Sclerostin, 1 hit
SMARTiView protein in SMART
SM00041 CT, 1 hit

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. AlignAdd to basket
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06576621V → L in CDD; affects protein secretion. 1 Publication1
Natural variantiVAR_06576721V → M in CDD; de novo mutation; affects protein secretion. 1 PublicationCorresponds to variant dbSNP:rs387907169EnsemblClinVar.1
Natural variantiVAR_063982167C → 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 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01018964 – 73RPPHHPFETK → WPGGRPPSRAPLST in isoform 2. 1 Publication10

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]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS11468.1 [Q9BQB4-1]
RefSeqiNP_079513.1, NM_025237.2 [Q9BQB4-1]
UniGeneiHs.349204

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K8PNMR-A25-213[»]
3SOVX-ray1.27Z115-121[»]
DisProtiDP00926
ProteinModelPortaliQ9BQB4
SMRiQ9BQB4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119186, 25 interactors
DIPiDIP-59407N
ELMiQ9BQB4
IntActiQ9BQB4, 101 interactors
STRINGi9606.ENSP00000301691

Chemistry databases

ChEMBLiCHEMBL3580487

Polymorphism and mutation databases

BioMutaiSOST
DMDMi20140220

Proteomic databases

PaxDbiQ9BQB4
PeptideAtlasiQ9BQB4
PRIDEiQ9BQB4
ProteomicsDBi78650
78651 [Q9BQB4-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi50964
DisGeNETi50964
EuPathDBiHostDB:ENSG00000167941.2
GeneCardsiSOST
GeneReviewsiSOST
HGNCiHGNC:13771 SOST
HPAiCAB025660
MalaCardsiSOST
MIMi122860 phenotype
239100 phenotype
269500 phenotype
605740 gene
neXtProtiNX_Q9BQB4
OpenTargetsiENSG00000167941
Orphaneti1513 Craniodiaphyseal dysplasia
3416 Hyperostosis corticalis generalisata
3152 Sclerosteosis
PharmGKBiPA37809
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVV4 Eukaryota
ENOG4111KFN LUCA
GeneTreeiENSGT00390000014900
HOGENOMiHOG000252934
HOVERGENiHBG003729
InParanoidiQ9BQB4
KOiK16834
OMAiDVSEYSC
OrthoDBiEOG091G13DX
PhylomeDBiQ9BQB4
TreeFamiTF353019

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-3772470 Negative regulation of TCF-dependent signaling by WNT ligand antagonists
SIGNORiQ9BQB4

Miscellaneous databases

EvolutionaryTraceiQ9BQB4
GeneWikiiSclerostin
SOST
GenomeRNAii50964
PROiPR:Q9BQB4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167941 Expressed in 46 organ(s), highest expression level in metanephros
CleanExiHS_SOST
GenevisibleiQ9BQB4 HS

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR006207 Cys_knot_C
IPR029034 Cystine-knot_cytokine
IPR008835 Sclerostin/SOSTDC1
IPR015665 SOST
PANTHERiPTHR14903 PTHR14903, 1 hit
PTHR14903:SF4 PTHR14903:SF4, 1 hit
PfamiView protein in Pfam
PF05463 Sclerostin, 1 hit
SMARTiView protein in SMART
SM00041 CT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSOST_HUMAN
AccessioniPrimary (citable) accession number: Q9BQB4
Secondary accession number(s): Q495N9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: September 12, 2018
This is version 149 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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