InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Htra1

Summary

InnateDB Protein

IDBP-210873.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Htra1

Protein Name

HtrA serine peptidase 1

Synonyms

AI429470; HTRA; L56; Prss11; RSPP11;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000006367

InnateDB Gene

IDBG-210871 (Htra1)

Protein Structure

UniProt Annotation

Function

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, but it is unclear whether it leads to the proteolytic degradation of TGF-beta proteins themselves (PubMed:18551132) or not (PubMed:14973287). 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. {ECO:0000269PubMed:14973287, ECO:0000269PubMed:15993670, ECO:0000269PubMed:18551132, ECO:0000269PubMed:22049084}.

Subcellular Localization

Secreted {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}. Note=Predominantly secreted. Also found associated with the plasma membrane. {ECO:0000250}.

Disease Associations

Tissue Specificity

In the brain, mainly expressed in cortical areas both in glial cells and neurons (at protein level). In bones, deposited in the matrix, with higher level in newly formed bone compared to fully calcified bone (at protein level). Also expressed in the tendons (at protein level). In the articular cartilage, detected only in the deepest zone of the joint cartilage. Not detected in the chondrocytes of the growth plate (at protein level). In an experimental arthritis model, at early disease stages, up-regulated in articular chondrocytes in the deep layers of the cartilage (at protein level). As arthritis progresses, chondrocyte expression expands toward the surface. {ECO:0000269PubMed:14973287, ECO:0000269PubMed:15993670, ECO:0000269PubMed:18551132}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003824	catalytic activity
GO:0004252	serine-type endopeptidase activity
GO:0005515	protein binding
GO:0005520	insulin-like growth factor binding
GO:0008236	serine-type peptidase activity

Biological Process

GO:0001558	regulation of cell growth
GO:0006508	proteolysis
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030514	negative regulation of BMP signaling pathway
GO:0050679	positive regulation of epithelial cell proliferation
GO:0050687	negative regulation of defense response to virus
GO:0097187	dentinogenesis

Cellular Component

GO:0005576	extracellular region
GO:0005829	cytosol
GO:0031012	extracellular matrix
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

MGI:1929076

InterPro

IPR000867 Insulin-like growth factor-binding protein, IGFBP
IPR001254 Peptidase S1
IPR001478 PDZ domain
IPR001940 Peptidase S1C
IPR002350 Kazal domain
IPR009003 Trypsin-like cysteine/serine peptidase domain

PFAM

PF00219
PF00089
PF00595
PF13180
PF00050
PF07648

PRINTS

PR00834

PIRSF

SMART

SM00121
SM00020
SM00228
SM00280

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt