Tchem HTRA1 Serine protease HTRA1

Protein Summary

Description

Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets. This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q92743
• D3DRE4
• Q9UNS5

Gene Name

• HTRA1

Ensembl ID

• ENST00000368984
• ENSP00000357980
• ENSG00000166033

Symbol

• HTRA
• PRSS11
• L56
• HtrA
• ARMD7
• ORF480
• PRSS11
• CARASIL
• CADASIL2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
PubMedID	0.99
transcription factor perturbation	0.94
biological term	0.92
gene perturbation	0.91

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Serine Protease / Serine Protease Htra1

Protein / Chaperone / Serine Protease Htra1

DTO Classes

Protein / Enzyme / Protease / Serine Protease / Serine Protease Htra1

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: 645.68   (req: < 5)

Gene RIFs: 203   (req: <= 3)

Antibodies: 260   (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: 645.68   (req: >= 5)

Gene RIFs: 203   (req: > 3)

Antibodies: 260   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

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

Active Ligands: 184

Tclin

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

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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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 (184)

Explore Active Ligands

1 – 10 of 184

CHEMBL4589967

HTRA1Tchem Enzyme

pIC50 : 9.58

CHEMBL4554156

HTRA1Tchem Enzyme

pIC50 : 9.53

CHEMBL4542635

HTRA1Tchem Enzyme

pIC50 : 9.52

CHEMBL4471645

HTRA1Tchem Enzyme

pIC50 : 9.52

CHEMBL4533165

HTRA1Tchem Enzyme

pIC50 : 9.52

CHEMBL4471714

HTRA1Tchem Enzyme

pIC50 : 9.46

CHEMBL4540590

HTRA1Tchem Enzyme

pIC50 : 9.4

CHEMBL4461666

HTRA1Tchem Enzyme

pIC50 : 9.4

CHEMBL4585025

HTRA1Tchem Enzyme

pIC50 : 9.4

CHEMBL4588306

HTRA1Tchem Enzyme

pIC50 : 9.4

Protein-Protein Interactions (95)

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1 – 10 of 95

• See Interactions on String-DB

TMEM25

Tdark

Novelty:  0.35505784

p_int:  0.999947389

p_ni:  0.000052256

p_wrong:  3.56e-7

Data Source:  BioPlex

SPINK4

Tdark

Family:  Enzyme

Novelty:  0.06706505

p_int:  0.999923967

p_ni:  0.00005544

p_wrong:  0.000020593

Score:  0.188

Data Source:  BioPlex,STRINGDB

REG4

Tbio

Novelty:  0.01123311

p_int:  0.999918533

p_ni:  0.00004259

p_wrong:  0.000038877

Score:  0.187

Data Source:  BioPlex,STRINGDB

AVP

Tbio

Novelty:  0.00016475

p_int:  0.99977256

p_ni:  0.000227369

p_wrong:  7.1e-8

Score:  0.197

Data Source:  BioPlex,STRINGDB

DEFB127

Tbio

Novelty:  0.18126756

p_int:  0.999498869

p_ni:  0.000501109

p_wrong:  2.2e-8

Score:  0.157

Data Source:  BioPlex,STRINGDB

MGAT4C

Tdark

Family:  Enzyme

Novelty:  0.19680806

p_int:  0.999183131

p_ni:  0.000780333

p_wrong:  0.000036536

Data Source:  BioPlex

MSMB

Tbio

Novelty:  0.00241546

p_int:  0.998882072

p_ni:  0.000533497

p_wrong:  0.000584431

Data Source:  BioPlex

NOG

Tbio

Novelty:  0.0010373

p_int:  0.998611655

p_ni:  0.000669766

p_wrong:  0.000718579

Data Source:  BioPlex

C12orf49

Tdark

Novelty:  0.56030929

p_int:  0.998195652

p_ni:  0.001650952

p_wrong:  0.000153397

Score:  0.173

Data Source:  BioPlex,STRINGDB

DEFA5

Tbio

Novelty:  0.00863727

p_int:  0.995929102

p_ni:  0.003926221

p_wrong:  0.000144677

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (2)

Reactome (2)

Degradation of the extracellular matrix (R-HSA-1474228)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Degradation of the extracellular matrix	111 targets	R-HSA-1474228
Reactome	Extracellular matrix organization	297 targets	R-HSA-1474244

Name	Explore in Pharos	Explore in Source
Degradation of the extracellular matrix	111 targets	R-HSA-1474228
Extracellular matrix organization	297 targets	R-HSA-1474244

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (20)

Functions (4)

Components (6)

Processes (10)

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1 – 4 of 4

GO Term	Evidence	Assigned by
serine-type endopeptidase activity	Inferred from Experiment (EXP)	Reactome
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
serine-type peptidase activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
insulin-like growth factor binding	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations (null)

No disease associations found

GWAS Traits (21)

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5

1 – 5 of 21

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
age-related macular degeneration	EFO_0001365	15	9	1	2.2	99.8
wet macular degeneration	EFO_0004683	5	3	0	2.3	98.2
atrophic macular degeneration	EFO_1001492	3	2	0	2.5	96.2
type II diabetes mellitus	EFO_0001360	8	5	4	1.1	90.8
disease progression measurement	EFO_0008336	1	1	0	2.1	83

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
age-related macular degeneration	EFO_0001365	1	2.2	99.8
wet macular degeneration	EFO_0004683	0	2.3	98.2
atrophic macular degeneration	EFO_1001492	0	2.5	96.2
type II diabetes mellitus	EFO_0001360	4	1.1	90.8
disease progression measurement	EFO_0008336	0	2.1	83

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Age-related macular degeneration
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Growth factor binding
Hydrolase

GWAS Trait Find Similar Targets

No Header	No Header
age-related macular degeneration
atrophic macular degeneration
autoimmune thyroid disease
birth weight
BMI-adjusted hip circumference
body height
central corneal thickness
cognitive function measurement
coronary artery disease
disease progression measurement

MGI Phenotype Find Similar Targets

No Header	No Header
skeleton phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	HtrA serine peptidase 1	VGNC:7229	450792
Macaque	HtrA serine peptidase 1		705855
Mouse	HtrA serine peptidase 1	MGI:1929076	56213
Rat	HtrA serine peptidase 1	RGD:69235	65164
Dog	HtrA serine peptidase 1	VGNC:41835	477852

Species	Name	OMA	EggNOG	Inparanoid
Chimp	HtrA serine peptidase 1
Macaque	HtrA serine peptidase 1
Mouse	HtrA serine peptidase 1
Rat	HtrA serine peptidase 1
Dog	HtrA serine peptidase 1

Publication Statistics

PubMed Score 645.68

PubMed score by year

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PubTator Score 327.15

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Related Publications

Text Mined References (246)

GeneRif Annotations (203)

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PMID	Year	Title