UniProt functional annotation for Q92743



	UniProt functional annotation for Q92743

UniProt code: Q92743.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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, 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. {ECO:0000269|PubMed:16377621, ECO:0000269|PubMed:20671064, ECO:0000269|PubMed:9852107}.

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). {ECO:0000250}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:21297635}. Secreted {ECO:0000269|PubMed:15208355, ECO:0000269|PubMed:9852107}. Cytoplasm, cytosol {ECO:0000269|PubMed:15208355, ECO:0000269|PubMed:20671064}. Note=Predominantly secreted (PubMed:15208355). Also found associated with the plasma membrane (PubMed:21297635). {ECO:0000269|PubMed:15208355, ECO:0000269|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). {ECO:0000269|PubMed:15208355, ECO:0000269|PubMed:16377621, ECO:0000269|PubMed:9852107}.

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). {ECO:0000269|PubMed:15208355}.

Domain: The IGFBP N-terminal domain mediates interaction with TSC2 substrate.

Disease: Macular degeneration, age-related, 7 (ARMD7) [MIM:610149]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:17053108, ECO:0000269|PubMed:17053109}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:600142]: A cerebrovascular disease characterized by non-hypertensive arteriopathy of cerebral small vessels with subcortical infarcts, alopecia, and spondylosis. Small cerebral arteries show arteriosclerotic changes, fibrous intimal proliferation, and hyaline degeneration with splitting of the intima and/or the internal elastic membrane. Neurologic features include progressive dementia, gait disturbances, extrapyramidal and pyramidal signs, and demyelination of the cerebral white matter with sparing of U fibers. {ECO:0000269|PubMed:19387015}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 2 (CADASIL2) [MIM:616779]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. {ECO:0000269|PubMed:26063658}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase S1C family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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, 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. {ECO:0000269\|PubMed:16377621, ECO:0000269\|PubMed:20671064, ECO:0000269\|PubMed:9852107}.


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). {ECO:0000250}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:21297635}. Secreted {ECO:0000269\|PubMed:15208355, ECO:0000269\|PubMed:9852107}. Cytoplasm, cytosol {ECO:0000269\|PubMed:15208355, ECO:0000269\|PubMed:20671064}. Note=Predominantly secreted (PubMed:15208355). Also found associated with the plasma membrane (PubMed:21297635). {ECO:0000269\|PubMed:15208355, ECO:0000269\|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). {ECO:0000269\|PubMed:15208355, ECO:0000269\|PubMed:16377621, ECO:0000269\|PubMed:9852107}.
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). {ECO:0000269\|PubMed:15208355}.
Domain:		The IGFBP N-terminal domain mediates interaction with TSC2 substrate.
Disease:		Macular degeneration, age-related, 7 (ARMD7) [MIM:610149]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269\|PubMed:17053108, ECO:0000269\|PubMed:17053109}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy (CARASIL) [MIM:600142]: A cerebrovascular disease characterized by non-hypertensive arteriopathy of cerebral small vessels with subcortical infarcts, alopecia, and spondylosis. Small cerebral arteries show arteriosclerotic changes, fibrous intimal proliferation, and hyaline degeneration with splitting of the intima and/or the internal elastic membrane. Neurologic features include progressive dementia, gait disturbances, extrapyramidal and pyramidal signs, and demyelination of the cerebral white matter with sparing of U fibers. {ECO:0000269\|PubMed:19387015}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 2 (CADASIL2) [MIM:616779]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. {ECO:0000269\|PubMed:26063658}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase S1C family. {ECO:0000305}.