Details of the Target

General Information of Target

Target ID LDTP09855
Target Name Serine protease HTRA1 (HTRA1)
Gene Name HTRA1
Gene ID 5654
Synonyms
HTRA; PRSS11; Serine protease HTRA1; EC 3.4.21.-; High-temperature requirement A serine peptidase 1; L56; Serine protease 11
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MNSDQDVALKLAQERAEIVAKYDRGREGAEIEPWEDADYLVYKVTDRFGFLHEEELPDHN
VAVERQKHLEIERTTKWLKMLKGWEKYKNTEKFHRRIYKGIPLQLRGEVWALLLEIPKMK
EETRDLYSKLKHRARGCSPDIRQIDLDVNRTFRDHIMFRDRYGVKQQSLFHVLAAYSIYN
TEVGYCQGMSQITALLLMYMNEEDAFWALVKLFSGPKHAMHGFFVQGFPKLLRFQEHHEK
ILNKFLSKLKQHLDSQEIYTSFYTMKWFFQCFLDRTPFTLNLRIWDIYIFEGERVLTAMS
YTILKLHKKHLMKLSMEELVEFFQETLAKDFFFEDDFVIEQLQISMTELKRAKLDLPEPG
KEDEYPKKPLGQLPPELQSWGVHHLSNGQRSVGRPSPLASGRRESGAPHRRHEHSPHPQS
RTGTPERAQPPRRKSVEEESKKLKDEADFQRKLPSGPQDSSRQYNHAAANQNSNATSNIR
KEFVPKWNKPSDVSATERTAKYTMEGKGRAAHPALAVTVPGPAEVRVSNVRPKMKALDAE
DGKRGSTASQYDNVPGPELDSGASVEEALERAYSQSPRHALYPPSPRKHAEPSSSPSKVS
NKFTFKVQPPSHARYPSQLDGEARGLAHPPSYSNPPVYHGNSPKHFPTANSSFASPQFSP
GTQLNPSRRPHGSTLSVSASPEKSYSRPSPLVLPSSRIEVLPVDTGAGGYSGNSGSPKNG
KLIIPPVDYLPDNRTWSEVSYTYRPETQGQSWTRDASRGNLPKYSAFQLAPFQDHGLPAV
SVDSPVRYKASPAAEDASPSGYPYSGPPPPAYHYRNRDGLSIQESVLL
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Peptidase S1C family
Subcellular location
Cell membrane
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.
TTD ID
T17642
Uniprot ID
Q92743
DrugMap ID
TT8POQR
Ensemble ID
ENST00000368984.8
HGNC ID
HGNC:9476
ChEMBL ID
CHEMBL4523419

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C155(1.13)  LDD0078  [1]
IA-alkyne
 Probe Info  		N.A.  LDD0162  [2]
TFBX
 Probe Info  		C37(0.00); C41(0.00); C155(0.00)  LDD0027  [3]
Acrolein
 Probe Info  		N.A.  LDD0217  [4]
Methacrolein
 Probe Info  		N.A.  LDD0218  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0020  ARS-1620 HCC44 C155(1.13)  LDD0078  [1]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [4]
 LDCM0022  KB02 A2058 C37(1.81)  LDD2253  [5]
 LDCM0023  KB03 A2058 C37(2.33)  LDD2670  [5]
 LDCM0024  KB05 UACC257 C37(1.55)  LDD3325  [5]
 LDCM0109  NEM HeLa N.A.  LDD0227  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Macrophage migration inhibitory factor (MIF) MIF family P14174
Serine protease HTRA1 (HTRA1) Peptidase S1C family Q92743
Serine protease HTRA4 (HTRA4) Peptidase S1C family P83105

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
4 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
5 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840