Tbio HSPG2 Basement membrane-specific heparan sulfate proteoglycan core protein

Protein Summary

Description

Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development. Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6. The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity. This gene encodes the perlecan protein, which consists of a core protein to which three long chains of glycosaminoglycans (heparan sulfate or chondroitin sulfate) are attached. The perlecan protein is a large multidomain proteoglycan that binds to and cross-links many extracellular matrix components and cell-surface molecules. It has been shown that this protein interacts with laminin, prolargin, collagen type IV, FGFBP1, FBLN2, FGF7 and transthyretin, etc., and it plays essential roles in multiple biological activities. Perlecan is a key component of the vascular extracellular matrix, where it helps to maintain the endothelial barrier function. It is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. It can also promote growth factor (e.g., FGF2) activity and thus stimulate endothelial growth and re-generation. It is a major component of basement membranes, where it is involved in the stabilization of other molecules as well as being involved with glomerular permeability to macromolecules and cell adhesion. Mutations in this gene cause Schwartz-Jampel syndrome type 1, Silverman-Handmaker type of dyssegmental dysplasia, and tardive dyskinesia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

Uniprot Accession IDs

• P98160
• Q16287
• Q5SZI3
• Q9H3V5
• HSPG

Gene Name

• HSPG2

Ensembl ID

• ENST00000374695
• ENSP00000363827
• ENSG00000142798

Symbol

• PLC
• SJA
• SJS
• HSPG
• SJS1
• PRCAN

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
cellular component	0.92
biological term	0.78
transcription factor	0.74
interacting protein	0.73

Protein Classes

PANTHER Classes

Protein / Receptor / Basement Membrane-specific Heparan Sulfate Proteoglycan Core Protein

Protein / Extracellular Matrix Protein / Extracellular Matrix Linker Protein / Basement Membrane-specific Heparan Sulfate Proteoglycan Core Protein

Protein / ... / Protease Inhibitor / Basement Membrane-specific Heparan Sulfate Proteoglycan Core Protein

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Basement Membrane-specific Heparan Sulfate Proteoglycan Core Protein

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: 683.49   (req: < 5)

Gene RIFs: 88   (req: <= 3)

Antibodies: 445   (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: 683.49   (req: >= 5)

Gene RIFs: 88   (req: > 3)

Antibodies: 445   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

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: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (263)

Explore Interacting Targets

1 – 10 of 263

• See Interactions on String-DB

TINAGL1

Tbio

Novelty:  0.05578199

p_int:  0.999999762

p_ni:  1.2e-8

p_wrong:  2.25e-7

Score:  0.591

Data Source:  BioPlex,STRINGDB

ADAM18

Tdark

Family:  Enzyme

Novelty:  0.22622379

p_int:  0.999991831

p_ni:  0.000008158

p_wrong:  1e-8

Data Source:  BioPlex

ZNF408

Tbio

Family:  TF

Novelty:  0.10649477

p_int:  0.999935375

p_ni:  0.000064569

p_wrong:  5.6e-8

Data Source:  BioPlex

H2BFWT

Tbio

Novelty:  0.16138632

p_int:  0.999488183

p_ni:  0.000125302

p_wrong:  0.000386515

Data Source:  BioPlex

NID1

Tbio

Novelty:  0.00169075

Score:  0.996

Data Source:  Reactome,STRINGDB

DAG1

Tbio

Family:  Enzyme

Novelty:  0.00149278

Score:  0.992

Data Source:  Reactome,STRINGDB

NID2

Tbio

Novelty:  0.01638372

Score:  0.991

Data Source:  Reactome,STRINGDB

FGF2

Tchem

Novelty:  0.00007856

Score:  0.99

Data Source:  STRINGDB

GPC1

Tbio

Novelty:  0.00293087

Score:  0.981

Data Source:  STRINGDB

GPC2

Tbio

Novelty:  0.02182363

Score:  0.977

Data Source:  STRINGDB

Nearest Tclin Targets (2)

Explore Nearest Tclin Targets

Downstream (2)

1 – 2 of 2

ITGB1

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  2

1: ECM-receptor interaction

2: Proteoglycans in cancer

VEGFA

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  1

1: Proteoglycans in cancer

Pathways (106)

Reactome (32)

KEGG (3)

PathwayCommons (8)

WikiPathways (63)

A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)

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1 – 5 of 32

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	A tetrasaccharide linker sequence is required for GAG synthesis	26 targets	R-HSA-1971475
Reactome	Amyloid fiber formation	79 targets	R-HSA-977225
Reactome	Chondroitin sulfate/dermatan sulfate metabolism	50 targets	R-HSA-1793185
Reactome	Defective B3GALT6 causes EDSP2 and SEMDJL1	20 targets	R-HSA-4420332
Reactome	Defective B3GAT3 causes JDSSDHD	20 targets	R-HSA-3560801

Name	Explore in Pharos	Explore in Source
A tetrasaccharide linker sequence is required for GAG synthesis	26 targets	R-HSA-1971475
Amyloid fiber formation	79 targets	R-HSA-977225
Chondroitin sulfate/dermatan sulfate metabolism	50 targets	R-HSA-1793185
Defective B3GALT6 causes EDSP2 and SEMDJL1	20 targets	R-HSA-4420332
Defective B3GAT3 causes JDSSDHD	20 targets	R-HSA-3560801

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (30)

Functions (5)

Components (10)

Processes (15)

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1 – 5 of 5

GO Term	Evidence	Assigned by
protein C-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
extracellular matrix structural constituent conferring compression resistance	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
integrin binding	Traceable Author Statement (TAS)	ARUK-UCL
low-density lipoprotein particle receptor binding	Traceable Author Statement (TAS)	ARUK-UCL
calcium ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations ()

No disease associations found

GWAS Traits (12)

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1 – 5 of 12

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte percentage of leukocytes	EFO_0007989	1	1	1		69.5
testosterone measurement	EFO_0004908	1	1	1		65.3
myeloid white cell count	EFO_0007988	1	1	1		64.4
leukocyte count	EFO_0004308	1	1	1		55.2
BMI-adjusted hip circumference	EFO_0008039	1	1	1		40.7

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 12

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte percentage of leukocytes	EFO_0007989	1		69.5
testosterone measurement	EFO_0004908	1		65.3
myeloid white cell count	EFO_0007988	1		64.4
leukocyte count	EFO_0004308	1		55.2
BMI-adjusted hip circumference	EFO_0008039	1		40.7

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Angiogenesis
Basement membrane
Calcium
Complete proteome
Direct protein sequencing
Disease mutation
Disulfide bond
EGF-like domain
Extracellular matrix

GWAS Trait Find Similar Targets

No Header	No Header
age at first birth measurement
atrial fibrillation
BMI-adjusted hip circumference
body height
hip circumference
leukocyte count
monocyte percentage of leukocytes
myeloid white cell count
neutrophil count
neutrophil percentage of leukocytes

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	heparan sulfate proteoglycan 2	VGNC:52978	100613114
Macaque	heparan sulfate proteoglycan 2		707213
Mouse	perlecan (heparan sulfate proteoglycan 2)	MGI:96257	15530
Dog	heparan sulfate proteoglycan 2	VGNC:41820	403440
Horse	heparan sulfate proteoglycan 2	VGNC:18898	100071701

Species	Name	OMA	EggNOG	Inparanoid
Chimp	heparan sulfate proteoglycan 2
Macaque	heparan sulfate proteoglycan 2
Mouse	perlecan (heparan sulfate proteoglycan 2)
Dog	heparan sulfate proteoglycan 2
Horse	heparan sulfate proteoglycan 2

Publication Statistics

PubMed Score 683.49

PubMed score by year

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PubTator Score 903.09

PubTator score by year

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Related Publications

Text Mined References (144)

GeneRif Annotations (88)

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PMID	Year	Title