Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:Q92743 HTRA1

Class:IdReferenceGeneProduct:56654
_chainChangeLogsignal peptide:1-22 added on Fri February 6 2015;chain:23-480 added on Fri February 6 2015
_displayNameUniProt:Q92743 HTRA1
_timestamp2026-02-20 21:30:47
chainsignal peptide:1-22
chain:23-480
checksumCA20A99480FB2330
commentFUNCTION 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.SUBUNIT Forms homotrimers. In the presence of substrate, may form higher-order multimers in a PDZ-independent manner. Interacts with TGF-beta family members, including BMP4, TGFB1, TGFB2, activin A and GDF5 (By similarity).INTERACTION Predominantly secreted (PubMed:15208355). Also found associated with the plasma membrane (PubMed:21297635).TISSUE SPECIFICITY Widely expressed, with strongest expression in placenta (at protein level). Secreted by synovial fibroblasts. Up-regulated in osteoarthritis and rheumatoid arthritis synovial fluids and cartilage as compared with non-arthritic (at protein level).DEVELOPMENTAL STAGE In the placenta, in the first trimester of gestation, low expression in the cells surrounding villi both in the inner layer of the cytotrophoblast and in the outer layer of the syncytiotrophoblast (at protein level). In the third trimester of gestation, very strong expression in the outer layer forming the syncytiotrophoblast and lower in the cytotrophoblast (at protein level).DOMAIN The IGFBP N-terminal domain mediates interaction with TSC2 substrate.DISEASE A variant in the HTRA1 promoter may be associated with increased risk for developing age-related macular degeneration (ARMD), a multifactorial eye disease and common cause of vision loss.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the peptidase S1C family.
descriptionrecommendedName: Serine protease HTRA1 ecNumber: 3.4.21.- alternativeName: High-temperature requirement A serine peptidase 1 alternativeName: L56 alternativeName: Serine protease 11
geneNameHTRA1
HTRA
PRSS11
identifierQ92743
isSequenceChangedFALSE
keyword3D-structure
Age-related macular degeneration
Cell membrane
Cytoplasm
Direct protein sequencing
Disease variant
Disulfide bond
Growth factor binding
Hydrolase
Membrane
Protease
Proteomics identification
Reference proteome
Secreted
Serine protease
Signal
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameHTRA1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8987874] ENSEMBL:ENSG00000166033 HTRA1 [Homo sapiens]
secondaryIdentifierHTRA1_HUMAN
D3DRE4
Q9UNS5
sequenceLength480
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:8855820] HTRA1 [extracellular region] [Homo sapiens]
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:Q92743 HTRA1 (56654)