Tclin SOST Sclerostin

Protein Summary

Description

Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation. Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Loss-of-function mutations in this gene are associated with an autosomal-recessive disorder, sclerosteosis, which causes progressive bone overgrowth. A deletion downstream of this gene, which causes reduced sclerostin expression, is associated with a milder form of the disorder called van Buchem disease. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9BQB4
• Q495N9

Gene Name

• SOST

Ensembl ID

• ENST00000301691
• ENSP00000301691
• ENSG00000167941

Symbol

• CDD
• VBCH
• DAND6
• SOST1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	0.92
biological process	0.66
microRNA	0.62
transcription factor	0.62
phenotype	0.61

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1068.59   (req: < 5)

Gene RIFs: 230   (req: <= 3)

Antibodies: 505   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1068.59   (req: >= 5)

Gene RIFs: 230   (req: > 3)

Antibodies: 505   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 11

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Approved Drugs (1)

Explore Approved Drugs

1 – 1 of 1

romosozumab

SOSTTclin

BINDING AGENT Kd: 11.7

Protein Data Bank (2)

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (11)

Reactome (4)

KEGG (2)

PathwayCommons (1)

WikiPathways (4)

Negative regulation of TCF-dependent signaling by WNT ligand antagonists (R-HSA-3772470)

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Items per page:

5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Negative regulation of TCF-dependent signaling by WNT ligand antagonists	15 targets	R-HSA-3772470
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by WNT	299 targets	R-HSA-195721
Reactome	TCF dependent signaling in response to WNT	204 targets	R-HSA-201681

Name	Explore in Pharos	Explore in Source
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	15 targets	R-HSA-3772470
Signal Transduction	2704 targets	R-HSA-162582
Signaling by WNT	299 targets	R-HSA-195721
TCF dependent signaling in response to WNT	204 targets	R-HSA-201681

Gene Ontology Terms (15)

Functions (2)

Components (4)

Processes (9)

Items per page:

10

1 – 2 of 2

GO Term	Evidence	Assigned by
transcription factor binding	Inferred from Direct Assay (IDA)	UniProtKB
heparin binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (135)

Explore Interacting Targets

1 – 10 of 135

• See Interactions on String-DB

LRP6

Tbio

Novelty: 0.00325624

p_int: 0.999955988

p_ni: 0.000044012

Score: 0.991

Data Source: BioPlex,Reactome,STRINGDB

CSH2

Tbio

Novelty: 0.00107578

p_int: 0.999809456

p_ni: 0.000190544

Score: 0.187

Data Source: BioPlex,STRINGDB

LRP5

Tbio

Novelty: 0.00102638

p_int: 0.999754372

p_ni: 0.000245628

Score: 0.995

Data Source: BioPlex,STRINGDB

SPOP

Tbio

Novelty: 0.00958399

p_int: 0.999651631

p_ni: 0.000348365

p_wrong: 4e-9

Score: 0.177

Data Source: BioPlex,STRINGDB

SRRT

Tbio

Novelty: 0.00367694

p_int: 0.999561049

p_ni: 0.000438951

Data Source: BioPlex

SIRT1

Tchem

Family: Epigenetic

Novelty: 0.00025951

p_int: 0.993145885

p_ni: 0.006854115

Score: 0.285

Data Source: BioPlex,STRINGDB

GTF2I

Tbio

Family: TF

Novelty: 0.00870461

p_int: 0.991539435

p_ni: 0.008460565

Score: 0.195

Data Source: BioPlex,STRINGDB

PSMG2

Tbio

Novelty: 0.07196402

p_int: 0.987815457

p_ni: 0.012184541

p_wrong: 2e-9

Data Source: BioPlex

DCAF5

Tdark

Novelty: 1.07807487

p_int: 0.971741069

p_ni: 0.02825893

Data Source: BioPlex

HERC2

Tbio

Family: Enzyme

Novelty: 0.05519779

p_int: 0.971281535

p_ni: 0.028718465

Data Source: BioPlex

Publication Statistics

PubMed Score  1068.59

PubMed score by year

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PubTator Score  418.32

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MQLPLALCLVCLLVHTAFRVVEGQGWQAFKNDATEIIPELGEYPEPPPELENNKTMNRAENGGRPPHHPF

1-70

ETKDVSEYSCRELHFTRYVTDGPCRSAKPVTELVCSGQCGPARLLPNAIGRGKWWRPSGPDFRCIPDRYR

70-140

AQRVQLLCPGGEAPRARKVRLVASCKCKRLTRFHNQSELKDFGTEAARPQKGRKPRPRARSAKANQAELE

140-210

NAY

210-213

MQLPLALCLVCLLVHTAFRVVEGQGWQAFKNDATEIIPELGEYPEPPPELENNKTMNRAENGGRPPHHPFETKDVSEYSCRELHFTRYVTDGPCRSAKPVTELVCSGQCGPARLLPNAIGRGKWWRPSGPDFRCIPDRYRAQRVQLLCPGGEAPRARKVRLVASCKCKRLTRFHNQSELKDFGTEAARPQKGRKPRPRARSAKANQAELENAY

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Uniprot Keyword

3D-structure
Alternative splicing
Complete proteome
Direct protein sequencing
Disease mutation
Disulfide bond
Extracellular matrix
Glycoprotein
Heparin-binding
Reference proteome