Details of the Target

General Information of Target

Target ID LDTP00773
Target Name Serine protease HTRA2, mitochondrial (HTRA2)
Gene Name HTRA2
Gene ID 27429
Synonyms
OMI; PRSS25; Serine protease HTRA2, mitochondrial; EC 3.4.21.108; High temperature requirement protein A2; HtrA2; Omi stress-regulated endoprotease; Serine protease 25; Serine proteinase OMI
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAPRAGRGAGWSLRAWRALGGIRWGRRPRLTPDLRALLTSGTSDPRARVTYGTPSLWAR
LSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTRSRAWLAVALGAGGAVLLL
LWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPAVVYIEILDRHPFLGREVPIS
NGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEAVVTAVDPVADIATLRIQTKEPL
PTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVSSAQRPARDLGLPQTNVEYIQTDAA
IDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRR
YIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQM
VQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE
Target Bioclass
Enzyme
Family
Peptidase S1C family
Subcellular location
Mitochondrion intermembrane space; Endoplasmic reticulum
Function
Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.
Uniprot ID
O43464
Ensemble ID
ENST00000258080.8
HGNC ID
HGNC:14348
ChEMBL ID
CHEMBL4523137

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
COLO320 SNV: p.A188P .
MFE280 SNV: p.D411E .
MOLT4 SNV: p.A230T .
NALM6 SNV: p.L173W .
NOMO1 SNV: p.A3V .
TOV21G SNV: p.A2S .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info  		K348(0.54)  LDD0277  [1]
DBIA
 Probe Info  		C71(0.94)  LDD1492  [2]
m-APA
 Probe Info  		N.A.  LDD2231  [3]
IPM
 Probe Info  		N.A.  LDD0025  [4]
TFBX
 Probe Info  		N.A.  LDD0027  [4]
NHS
 Probe Info  		N.A.  LDD0010  [5]
PAL-AfBPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C087
 Probe Info  		7.01  LDD1779  [6]
C278
 Probe Info  		50.56  LDD1948  [6]
C280
 Probe Info  		10.34  LDD1950  [6]
C282
 Probe Info  		17.51  LDD1952  [6]
C284
 Probe Info  		23.26  LDD1954  [6]
C313
 Probe Info  		13.74  LDD1980  [6]
C314
 Probe Info  		13.55  LDD1981  [6]
C338
 Probe Info  		10.70  LDD2001  [6]
VE-P
 Probe Info  		N.A.  LDD0396  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0215  AC10 HEK-293T C71(1.03)  LDD1508  [2]
 LDCM0226  AC11 HEK-293T C71(1.01)  LDD1509  [2]
 LDCM0270  AC15 HEK-293T C71(0.99)  LDD1513  [2]
 LDCM0277  AC18 HEK-293T C71(1.10)  LDD1516  [2]
 LDCM0278  AC19 HEK-293T C71(1.13)  LDD1517  [2]
 LDCM0279  AC2 HEK-293T C71(0.96)  LDD1518  [2]
 LDCM0281  AC21 HEK-293T C71(1.05)  LDD1520  [2]
 LDCM0283  AC23 HEK-293T C71(0.95)  LDD1522  [2]
 LDCM0284  AC24 HEK-293T C71(1.06)  LDD1523  [2]
 LDCM0286  AC26 HEK-293T C71(1.02)  LDD1525  [2]
 LDCM0287  AC27 HEK-293T C71(1.09)  LDD1526  [2]
 LDCM0289  AC29 HEK-293T C71(1.08)  LDD1528  [2]
 LDCM0290  AC3 HEK-293T C71(1.02)  LDD1529  [2]
 LDCM0292  AC31 HEK-293T C71(0.97)  LDD1531  [2]
 LDCM0293  AC32 HEK-293T C71(1.04)  LDD1532  [2]
 LDCM0295  AC34 HEK-293T C71(1.08)  LDD1534  [2]
 LDCM0296  AC35 HEK-293T C71(1.06)  LDD1535  [2]
 LDCM0298  AC37 HEK-293T C71(0.98)  LDD1537  [2]
 LDCM0300  AC39 HEK-293T C71(1.10)  LDD1539  [2]
 LDCM0302  AC40 HEK-293T C71(1.09)  LDD1541  [2]
 LDCM0304  AC42 HEK-293T C71(1.08)  LDD1543  [2]
 LDCM0305  AC43 HEK-293T C71(1.06)  LDD1544  [2]
 LDCM0307  AC45 HEK-293T C71(0.99)  LDD1546  [2]
 LDCM0309  AC47 HEK-293T C71(1.08)  LDD1548  [2]
 LDCM0310  AC48 HEK-293T C71(1.05)  LDD1549  [2]
 LDCM0312  AC5 HEK-293T C71(0.99)  LDD1551  [2]
 LDCM0313  AC50 HEK-293T C71(1.09)  LDD1552  [2]
 LDCM0314  AC51 HEK-293T C71(1.05)  LDD1553  [2]
 LDCM0316  AC53 HEK-293T C71(1.05)  LDD1555  [2]
 LDCM0318  AC55 HEK-293T C71(0.98)  LDD1557  [2]
 LDCM0319  AC56 HEK-293T C71(1.04)  LDD1558  [2]
 LDCM0321  AC58 HEK-293T C71(1.11)  LDD1560  [2]
 LDCM0322  AC59 HEK-293T C71(0.99)  LDD1561  [2]
 LDCM0325  AC61 HEK-293T C71(1.01)  LDD1564  [2]
 LDCM0327  AC63 HEK-293T C71(1.09)  LDD1566  [2]
 LDCM0328  AC64 HEK-293T C71(1.03)  LDD1567  [2]
 LDCM0334  AC7 HEK-293T C71(0.96)  LDD1568  [2]
 LDCM0345  AC8 HEK-293T C71(1.12)  LDD1569  [2]
 LDCM0248  AKOS034007472 HEK-293T C71(0.97)  LDD1511  [2]
 LDCM0275  AKOS034007705 HEK-293T C71(1.14)  LDD1514  [2]
 LDCM0371  CL102 HEK-293T C71(0.94)  LDD1575  [2]
 LDCM0372  CL103 HEK-293T C71(1.00)  LDD1576  [2]
 LDCM0375  CL106 HEK-293T C71(0.96)  LDD1579  [2]
 LDCM0376  CL107 HEK-293T C71(0.87)  LDD1580  [2]
 LDCM0379  CL11 HEK-293T C71(1.26)  LDD1583  [2]
 LDCM0380  CL110 HEK-293T C71(1.21)  LDD1584  [2]
 LDCM0381  CL111 HEK-293T C71(0.92)  LDD1585  [2]
 LDCM0384  CL114 HEK-293T C71(1.02)  LDD1588  [2]
 LDCM0385  CL115 HEK-293T C71(0.99)  LDD1589  [2]
 LDCM0388  CL118 HEK-293T C71(1.03)  LDD1592  [2]
 LDCM0389  CL119 HEK-293T C71(1.02)  LDD1593  [2]
 LDCM0390  CL12 HEK-293T C71(1.20)  LDD1594  [2]
 LDCM0393  CL122 HEK-293T C71(0.97)  LDD1597  [2]
 LDCM0394  CL123 HEK-293T C71(0.94)  LDD1598  [2]
 LDCM0397  CL126 HEK-293T C71(0.91)  LDD1601  [2]
 LDCM0398  CL127 HEK-293T C71(0.92)  LDD1602  [2]
 LDCM0401  CL14 HEK-293T C71(1.06)  LDD1605  [2]
 LDCM0402  CL15 HEK-293T C71(1.17)  LDD1606  [2]
 LDCM0405  CL18 HEK-293T C71(1.14)  LDD1609  [2]
 LDCM0406  CL19 HEK-293T C71(1.12)  LDD1610  [2]
 LDCM0407  CL2 HEK-293T C71(1.14)  LDD1611  [2]
 LDCM0409  CL21 HEK-293T C71(1.39)  LDD1613  [2]
 LDCM0411  CL23 HEK-293T C71(1.23)  LDD1615  [2]
 LDCM0412  CL24 HEK-293T C71(1.17)  LDD1616  [2]
 LDCM0414  CL26 HEK-293T C71(0.98)  LDD1618  [2]
 LDCM0415  CL27 HEK-293T C71(0.93)  LDD1619  [2]
 LDCM0418  CL3 HEK-293T C71(1.20)  LDD1622  [2]
 LDCM0419  CL30 HEK-293T C71(1.10)  LDD1623  [2]
 LDCM0420  CL31 HEK-293T C71(1.08)  LDD1624  [2]
 LDCM0422  CL33 HEK-293T C71(1.37)  LDD1626  [2]
 LDCM0424  CL35 HEK-293T C71(1.14)  LDD1628  [2]
 LDCM0425  CL36 HEK-293T C71(1.03)  LDD1629  [2]
 LDCM0428  CL39 HEK-293T C71(1.20)  LDD1632  [2]
 LDCM0432  CL42 HEK-293T C71(1.05)  LDD1636  [2]
 LDCM0433  CL43 HEK-293T C71(0.99)  LDD1637  [2]
 LDCM0435  CL45 HEK-293T C71(1.25)  LDD1639  [2]
 LDCM0437  CL47 HEK-293T C71(1.10)  LDD1641  [2]
 LDCM0438  CL48 HEK-293T C71(0.99)  LDD1642  [2]
 LDCM0441  CL50 HEK-293T C71(1.52)  LDD1645  [2]
 LDCM0445  CL54 HEK-293T C71(1.24)  LDD1648  [2]
 LDCM0446  CL55 HEK-293T C71(1.05)  LDD1649  [2]
 LDCM0448  CL57 HEK-293T C71(1.49)  LDD1651  [2]
 LDCM0450  CL59 HEK-293T C71(1.25)  LDD1653  [2]
 LDCM0451  CL6 HEK-293T C71(1.26)  LDD1654  [2]
 LDCM0452  CL60 HEK-293T C71(1.15)  LDD1655  [2]
 LDCM0454  CL62 HEK-293T C71(1.02)  LDD1657  [2]
 LDCM0455  CL63 HEK-293T C71(1.02)  LDD1658  [2]
 LDCM0458  CL66 HEK-293T C71(1.15)  LDD1661  [2]
 LDCM0459  CL67 HEK-293T C71(1.08)  LDD1662  [2]
 LDCM0461  CL69 HEK-293T C71(1.41)  LDD1664  [2]
 LDCM0462  CL7 HEK-293T C71(1.06)  LDD1665  [2]
 LDCM0464  CL71 HEK-293T C71(1.20)  LDD1667  [2]
 LDCM0465  CL72 HEK-293T C71(1.08)  LDD1668  [2]
 LDCM0467  CL74 HEK-293T C71(1.12)  LDD1670  [2]
 LDCM0471  CL78 HEK-293T C71(1.09)  LDD1674  [2]
 LDCM0472  CL79 HEK-293T C71(1.04)  LDD1675  [2]
 LDCM0475  CL81 HEK-293T C71(1.12)  LDD1678  [2]
 LDCM0477  CL83 HEK-293T C71(1.16)  LDD1680  [2]
 LDCM0478  CL84 HEK-293T C71(1.13)  LDD1681  [2]
 LDCM0480  CL86 HEK-293T C71(0.90)  LDD1683  [2]
 LDCM0481  CL87 HEK-293T C71(1.01)  LDD1684  [2]
 LDCM0484  CL9 HEK-293T C71(1.34)  LDD1687  [2]
 LDCM0485  CL90 HEK-293T C71(1.39)  LDD1688  [2]
 LDCM0486  CL91 HEK-293T C71(0.58)  LDD1689  [2]
 LDCM0488  CL93 HEK-293T C71(1.29)  LDD1691  [2]
 LDCM0490  CL95 HEK-293T C71(1.36)  LDD1693  [2]
 LDCM0491  CL96 HEK-293T C71(1.13)  LDD1694  [2]
 LDCM0493  CL98 HEK-293T C71(1.14)  LDD1696  [2]
 LDCM0494  CL99 HEK-293T C71(1.13)  LDD1697  [2]
 LDCM0495  E2913 HEK-293T C71(1.01)  LDD1698  [2]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C71(1.71)  LDD1702  [8]
 LDCM0468  Fragment33 HEK-293T C71(1.13)  LDD1671  [2]
 LDCM0427  Fragment51 HEK-293T C71(0.90)  LDD1631  [2]
 LDCM0022  KB02 HEK-293T C71(0.94)  LDD1492  [2]
 LDCM0023  KB03 HEK-293T C71(1.09)  LDD1497  [2]
 LDCM0024  KB05 HEK-293T C71(1.10)  LDD1502  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 18 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
26S proteasome regulatory subunit 6A (PSMC3) AAA ATPase family P17980
NADH dehydrogenase 1 alpha subcomplex subunit 13 (NDUFA13) Complex I NDUFA13 subunit family Q9P0J0
Eukaryotic translation initiation factor 3 subunit F (EIF3F) EIF-3 subunit F family O00303
Baculoviral IAP repeat-containing protein 7 (BIRC7) IAP family Q96CA5
E3 ubiquitin-protein ligase XIAP (XIAP) IAP family P98170
Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2) L-isoaspartyl/D-aspartyl protein methyltransferase family Q9NV79
Ubiquitin thioesterase OTUB1 (OTUB1) Peptidase C65 family Q96FW1
Inactive ubiquitin thioesterase OTULINL (OTULINL) Peptidase C65 family Q9NUU6
MPN domain-containing protein (MPND) Peptidase M67 family Q8N594
E3 SUMO-protein ligase PIAS1 (PIAS1) PIAS family O75925
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) STE Ser/Thr protein kinase family Q99683
E3 ubiquitin-protein ligase MYLIP (MYLIP) . Q8WY64
E3 ubiquitin-protein ligase RNF138 (RNF138) . Q8WVD3
E3 ubiquitin-protein ligase RNF183 (RNF183) . Q96D59
LON peptidase N-terminal domain and RING finger protein 2 (LONRF2) . Q1L5Z9
NEDD4-like E3 ubiquitin-protein ligase WWP2 (WWP2) . O00308
pre-mRNA splicing regulator USH1G (USH1G) . Q495M9
Probable E3 ubiquitin-protein ligase MARCHF10 (MARCHF10) . Q8NA82
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Alpha-crystallin A chain (CRYAA) Small heat shock protein (HSP20) family P02489
Transcription factor
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Krueppel-like factor 3 (KLF3) Krueppel C2H2-type zinc-finger protein family P57682
Zinc finger and SCAN domain-containing protein 9 (ZSCAN9) Krueppel C2H2-type zinc-finger protein family O15535
Zinc finger protein 232 (ZNF232) Krueppel C2H2-type zinc-finger protein family Q9UNY5
Zinc finger protein 500 (ZNF500) Krueppel C2H2-type zinc-finger protein family O60304
Paired mesoderm homeobox protein 2A (PHOX2A) Paired homeobox family O14813
DNA-binding protein inhibitor ID-2 (ID2) . Q02363
Neurogenic differentiation factor 1 (NEUROD1) . Q13562
Zinc finger and BTB domain-containing protein 25 (ZBTB25) . P24278
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tumor necrosis factor ligand superfamily member 15 (TNFSF15) Tumor necrosis factor family O95150
Other
Click To Hide/Show 20 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Endophilin-B2 (SH3GLB2) Endophilin family Q9NR46
Centromere protein V (CENPV) Gfa family Q7Z7K6
HAUS augmin-like complex subunit 7 (HAUS7) HAUS7 family Q99871
Keratin, type I cuticular Ha3-II (KRT33B) Intermediate filament family Q14525
Keratin, type I cytoskeletal 19 (KRT19) Intermediate filament family P08727
Kinesin light chain 3 (KLC3) Kinesin light chain family Q6P597
PIH1 domain-containing protein 2 (PIH1D2) PIH1 family Q8WWB5
RUS family member 1 (RUSF1) RUS1 family Q96GQ5
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 (SMARCD1) SMARCD family Q96GM5
Protein TASOR 2 (TASOR2) TASOR family Q5VWN6
CST complex subunit TEN1 (TEN1) TEN1 family Q86WV5
Tetratricopeptide repeat protein 19, mitochondrial (TTC19) TTC19 family Q6DKK2
Vacuolar protein sorting-associated protein 37A (VPS37A) VPS37 family Q8NEZ2
BTB/POZ domain-containing protein KCTD17 (KCTD17) . Q8N5Z5
Enkurin (ENKUR) . Q8TC29
Kelch-like protein 20 (KLHL20) . Q9Y2M5
Protein phosphatase 1 regulatory inhibitor subunit 16B (PPP1R16B) . Q96T49
RING1 and YY1-binding protein (RYBP) . Q8N488
Splicing regulator RBM11 (RBM11) . P57052
Suppressor of cytokine signaling 4 (SOCS4) . Q8WXH5

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
3 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
4 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
5 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
6 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
7 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
8 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761