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UniProtKB - Q9BQB4 (SOST_HUMAN)

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Protein

Sclerostin

Gene

SOST

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

  • heparin binding Source: UniProtKB-KW
  • transcription factor binding Source: UniProtKB
Complete GO annotation...

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 complex assembly Source: BHF-UCL
  • negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification Source: BHF-UCL
  • ossification Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • response to mechanical stimulus Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:13771. SOST.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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:rs387907169Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi50964.
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.

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.
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

Show more details

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi119186. 23 interactors.
DIPiDIP-59407N.
IntActiQ9BQB4. 99 interactors.
STRINGi9606.ENSP00000301691.

Structurei

Secondary structure

1213
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi78 – 80Combined sources3
Beta strandi82 – 87Combined sources6
Beta strandi95 – 98Combined sources4
Beta strandi100 – 105Combined sources6
Beta strandi139 – 147Combined sources9
Beta strandi155 – 162Combined sources8

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...

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:SF8. PTHR14903:SF8. 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:rs387907169Ensembl.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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: May 10, 2017
This is version 141 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

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