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Showing Protein Serine protease HTRA1 (HMDBP14536)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14536
Secondary Accession Numbers None
Name Serine protease HTRA1
Synonyms
  1. High-temperature requirement A serine peptidase 1
  2. L56
  3. Serine protease 11
Gene Name HTRA1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
negative regulation of transforming growth factor beta receptor signaling pathway
dentinogenesis
chorionic trophoblast cell differentiation
negative regulation of defense response to virus
extracellular matrix disassembly
negative regulation of BMP signaling pathway
positive regulation of epithelial cell proliferation
placenta development
proteolysis
Cellular Component
extracellular region
cytosol
collagen-containing extracellular matrix
extracellular space
plasma membrane
extracellular vesicular exosome
Molecular Function
identical protein binding
serine-type endopeptidase activity
serine-type peptidase activity
insulin-like growth factor binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 480
Molecular Weight 51286.415
Theoretical pI 7.826
Pfam Domain Function
Signals
  • 1-22;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q92743
UniProtKB/Swiss-Prot Entry Name HTRA1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Hu SI, Carozza M, Klein M, Nantermet P, Luk D, Crowl RM: Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage. J Biol Chem. 1998 Dec 18;273(51):34406-12. doi: 10.1074/jbc.273.51.34406. [PubMed:9852107 ]
  2. Zumbrunn J, Trueb B: Primary structure of a putative serine protease specific for IGF-binding proteins. FEBS Lett. 1996 Dec 2;398(2-3):187-92. doi: 10.1016/s0014-5793(96)01229-x. [PubMed:8977104 ]
  3. De Luca A, De Falco M, Fedele V, Cobellis L, Mastrogiacomo A, Laforgia V, Tuduce IL, Campioni M, Giraldi D, Paggi MG, Baldi A: The serine protease HtrA1 is upregulated in the human placenta during pregnancy. J Histochem Cytochem. 2004 Jul;52(7):885-92. doi: 10.1369/jhc.3A6186.2004. [PubMed:15208355 ]
  4. Grau S, Richards PJ, Kerr B, Hughes C, Caterson B, Williams AS, Junker U, Jones SA, Clausen T, Ehrmann M: The role of human HtrA1 in arthritic disease. J Biol Chem. 2006 Mar 10;281(10):6124-9. doi: 10.1074/jbc.M500361200. Epub 2005 Dec 22. [PubMed:16377621 ]
  5. Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS, Snyder M, Barnstable C, Pang CP, Hoh J: HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006 Nov 10;314(5801):989-92. doi: 10.1126/science.1133807. Epub 2006 Oct 19. [PubMed:17053108 ]
  6. Campioni M, Severino A, Manente L, Tuduce IL, Toldo S, Caraglia M, Crispi S, Ehrmann M, He X, Maguire J, De Falco M, De Luca A, Shridhar V, Baldi A: The serine protease HtrA1 specifically interacts and degrades the tuberous sclerosis complex 2 protein. Mol Cancer Res. 2010 Sep;8(9):1248-60. doi: 10.1158/1541-7786.MCR-09-0473. Epub 2010 Jul 29. [PubMed:20671064 ]
  7. Verdura E, Herve D, Scharrer E, Amador Mdel M, Guyant-Marechal L, Philippi A, Corlobe A, Bergametti F, Gazal S, Prieto-Morin C, Beaufort N, Le Bail B, Viakhireva I, Dichgans M, Chabriat H, Haffner C, Tournier-Lasserve E: Heterozygous HTRA1 mutations are associated with autosomal dominant cerebral small vessel disease. Brain. 2015 Aug;138(Pt 8):2347-58. doi: 10.1093/brain/awv155. Epub 2015 Jun 10. [PubMed:26063658 ]
  8. Truebestein L, Tennstaedt A, Monig T, Krojer T, Canellas F, Kaiser M, Clausen T, Ehrmann M: Substrate-induced remodeling of the active site regulates human HTRA1 activity. Nat Struct Mol Biol. 2011 Mar;18(3):386-8. doi: 10.1038/nsmb.2013. Epub 2011 Feb 6. [PubMed:21297635 ]