Serine protease HTRA1

HTRA1
Identifiers
Aliases	HTRA1, ARMD7, CARASIL, HtrA, L56, ORF480, PRSS11, CADASIL2, HtrA serine peptidase 1
External IDs	OMIM: 602194; MGI: 1929076; GeneCards: HTRA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JOA, 2YTW, 3NUM, 3NWU, 3NZI, 3TJN, 3TJO, 3TJQ
Gene location (Human) Chr. Chromosome 10 (human) Band 10q26.13 Start 122,458,551 bp End 122,514,907 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 F3 Start 130,537,841 bp End 130,587,390 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tendon of biceps brachii glomerulus metanephric glomerulus Descending thoracic aorta stromal cell of endometrium ascending aorta synovial membrane middle frontal gyrus synovial joint putamen Top expressed in decidua epithelium of lens facial motor nucleus gastrula cumulus cell calvaria umbilical cord ascending aorta motor neuron tunica media of zone of aorta More reference expression data BioGPS More reference expression data
Gene ontology Molecular function insulin-like growth factor binding growth factor binding peptidase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity protein binding identical protein binding Cellular component cytoplasm cytosol membrane extracellular matrix plasma membrane extracellular exosome extracellular region extracellular space collagen-containing extracellular matrix Biological process negative regulation of defense response to virus chorionic trophoblast cell differentiation positive regulation of epithelial cell proliferation placenta development dentinogenesis negative regulation of transforming growth factor beta receptor signaling pathway proteolysis negative regulation of BMP signaling pathway regulation of cell growth extracellular matrix disassembly Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 5654 56213 Ensembl ENSG00000166033 ENSMUSG00000006205 UniProt Q92743 Q9R118 RefSeq (mRNA) NM_002775 NM_019564 RefSeq (protein) NP_002766 NP_062510 Location (UCSC) Chr 10: 122.46 – 122.51 Mb Chr 7: 130.54 – 130.59 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Serine protease HTRA1 is an enzyme that in humans is encoded by the HTRA1 gene.

Structure

The HTRA1 protein is composed of four distinct protein domains. They are from amino-terminus to carboxyl-terminus an Insulin-like growth factor binding domain, a kazal domain, a trypsin-like peptidase domain and a PDZ domain.

This gene encodes a member of the trypsin family of serine proteases.

Function

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.

Clinical significance

Mutations of this gene are responsible for the development of CARASIL, a genetic form of cerebral vasculopathy.

External links

• GeneReviews/NCBI/NIH/UW entry on CARASIL Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, Maeda Syndrome
• OMIM entries on CARASIL

Further reading

• Bradley DT, Zipfel PF, Hughes AE (June 2011). "Complement in age-related macular degeneration: a focus on function". Eye. 25 (6). London, England: 683–693. doi:10.1038/eye.2011.37. PMC 3178140. PMID 21394116.
• Zurawa-Janicka D, Narkiewicz J, Lipińska B (2007). "[Characterization of the HtrA family of proteins]". Postepy Biochemii. 53 (1): 27–36. PMID 17718385.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–358. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Zumbrunn J, Trueb B (1998). "Localization of the gene for a serine protease with IGF-binding domain (PRSS11) to human chromosome 10q25.3-q26.2". Genomics. 45 (2): 461–462. doi:10.1006/geno.1997.4953. PMID 9344681.
• Hu SI, Carozza M, Klein M, Nantermet P, Luk D, Crowl RM (December 1998). "Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage". The Journal of Biological Chemistry. 273 (51): 34406–34412. doi:10.1074/jbc.273.51.34406. PMID 9852107.
• Baldi A, De Luca A, Morini M, Battista T, Felsani A, Baldi F, et al. (September 2002). "The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells". Oncogene. 21 (43): 6684–6688. doi:10.1038/sj.onc.1205911. PMID 12242667. S2CID 9021435.
• Nie GY, Hampton A, Li Y, Findlay JK, Salamonsen LA (April 2003). "Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2". The Biochemical Journal. 371 (Pt 1): 39–48. doi:10.1042/BJ20021569. PMC 1223265. PMID 12513693.
• De Luca A, De Falco M, Severino A, Campioni M, Santini D, Baldi F, et al. (October 2003). "Distribution of the serine protease HtrA1 in normal human tissues". The Journal of Histochemistry and Cytochemistry. 51 (10): 1279–1284. doi:10.1177/002215540305101004. PMID 14500695. S2CID 19726897.
• Chien J, Staub J, Hu SI, Erickson-Johnson MR, Couch FJ, Smith DI, et al. (February 2004). "A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer". Oncogene. 23 (8): 1636–1644. doi:10.1038/sj.onc.1207271. PMID 14716297.
• Oka C, Tsujimoto R, Kajikawa M, Koshiba-Takeuchi K, Ina J, Yano M, et al. (March 2004). "HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins". Development. 131 (5). Cambridge, England: 1041–1053. doi:10.1242/dev.00999. PMID 14973287. S2CID 27495047.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, et al. (July 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–1332. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Grau S, Baldi A, Bussani R, Tian X, Stefanescu R, Przybylski M, et al. (April 2005). "Implications of the serine protease HtrA1 in amyloid precursor protein processing". Proceedings of the National Academy of Sciences of the United States of America. 102 (17): 6021–6026. doi:10.1073/pnas.0501823102. PMC 1087941. PMID 15855271.
• Ozturk A, Desai PP, Minster RL, Dekosky ST, Kamboh MI (2005). "Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's disease". Neurobiology of Aging. 26 (8): 1161–1165. doi:10.1016/j.neurobiolaging.2004.11.001. PMID 15917099. S2CID 10878355.
• Grau S, Richards PJ, Kerr B, Hughes C, Caterson B, Williams AS, et al. (March 2006). "The role of human HtrA1 in arthritic disease". The Journal of Biological Chemistry. 281 (10): 6124–6129. doi:10.1074/jbc.M500361200. PMID 16377621.
• Bowden MA, Di Nezza-Cossens LA, Jobling T, Salamonsen LA, Nie G (October 2006). "Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer". Gynecologic Oncology. 103 (1): 253–260. doi:10.1016/j.ygyno.2006.03.006. PMID 16650464.
• Chien J, Aletti G, Baldi A, Catalano V, Muretto P, Keeney GL, et al. (July 2006). "Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity". The Journal of Clinical Investigation. 116 (7): 1994–2004. doi:10.1172/JCI27698. PMC 1474818. PMID 16767218.
• Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, et al. (November 2006). "HTRA1 promoter polymorphism in wet age-related macular degeneration". Science. 314 (5801). New York, N.Y.: 989–992. doi:10.1126/science.1133807. PMID 17053108. S2CID 85725181.