Details of the Target

General Information of Target

Target ID LDTP01814
Target Name Alpha-2-macroglobulin (A2M)
Gene Name A2M
Gene ID 2
Synonyms
CPAMD5; Alpha-2-macroglobulin; Alpha-2-M; C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGKNKLLHPSLVLLLLVLLPTDASVSGKPQYMVLVPSLLHTETTEKGCVLLSYLNETVTV
SASLESVRGNRSLFTDLEAENDVLHCVAFAVPKSSSNEEVMFLTVQVKGPTQEFKKRTTV
MVKNEDSLVFVQTDKSIYKPGQTVKFRVVSMDENFHPLNELIPLVYIQDPKGNRIAQWQS
FQLEGGLKQFSFPLSSEPFQGSYKVVVQKKSGGRTEHPFTVEEFVLPKFEVQVTVPKIIT
ILEEEMNVSVCGLYTYGKPVPGHVTVSICRKYSDASDCHGEDSQAFCEKFSGQLNSHGCF
YQQVKTKVFQLKRKEYEMKLHTEAQIQEEGTVVELTGRQSSEITRTITKLSFVKVDSHFR
QGIPFFGQVRLVDGKGVPIPNKVIFIRGNEANYYSNATTDEHGLVQFSINTTNVMGTSLT
VRVNYKDRSPCYGYQWVSEEHEEAHHTAYLVFSPSKSFVHLEPMSHELPCGHTQTVQAHY
ILNGGTLLGLKKLSFYYLIMAKGGIVRTGTHGLLVKQEDMKGHFSISIPVKSDIAPVARL
LIYAVLPTGDVIGDSAKYDVENCLANKVDLSFSPSQSLPASHAHLRVTAAPQSVCALRAV
DQSVLLMKPDAELSASSVYNLLPEKDLTGFPGPLNDQDNEDCINRHNVYINGITYTPVSS
TNEKDMYSFLEDMGLKAFTNSKIRKPKMCPQLQQYEMHGPEGLRVGFYESDVMGRGHARL
VHVEEPHTETVRKYFPETWIWDLVVVNSAGVAEVGVTVPDTITEWKAGAFCLSEDAGLGI
SSTASLRAFQPFFVELTMPYSVIRGEAFTLKATVLNYLPKCIRVSVQLEASPAFLAVPVE
KEQAPHCICANGRQTVSWAVTPKSLGNVNFTVSAEALESQELCGTEVPSVPEHGRKDTVI
KPLLVEPEGLEKETTFNSLLCPSGGEVSEELSLKLPPNVVEESARASVSVLGDILGSAMQ
NTQNLLQMPYGCGEQNMVLFAPNIYVLDYLNETQQLTPEIKSKAIGYLNTGYQRQLNYKH
YDGSYSTFGERYGRNQGNTWLTAFVLKTFAQARAYIFIDEAHITQALIWLSQRQKDNGCF
RSSGSLLNNAIKGGVEDEVTLSAYITIALLEIPLTVTHPVVRNALFCLESAWKTAQEGDH
GSHVYTKALLAYAFALAGNQDKRKEVLKSLNEEAVKKDNSVHWERPQKPKAPVGHFYEPQ
APSAEVEMTSYVLLAYLTAQPAPTSEDLTSATNIVKWITKQQNAQGGFSSTQDTVVALHA
LSKYGAATFTRTGKAAQVTIQSSGTFSSKFQVDNNNRLLLQQVSLPELPGEYSMKVTGEG
CVYLQTSLKYNILPEKEEFPFALGVQTLPQTCDEPKAHTSFQISLSVSYTGSRSASNMAI
VDVKMVSGFIPLKPTVKMLERSNHVSRTEVSSNHVLIYLDKVSNQTLSLFFTVLQDVPVR
DLKPAIVKVYDYYETDEFAIAEYNAPCSKDLGNA
Target Bioclass
Other
Family
Protease inhibitor I39 (alpha-2-macroglobulin) family
Subcellular location
Secreted
Function
Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
Uniprot ID
P01023
Ensemble ID
ENST00000318602.12
HGNC ID
HGNC:7
ChEMBL ID
CHEMBL4295690

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 12 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
YN-1
 Probe Info  		100.00  LDD0444  [2]
YN-4
 Probe Info  		100.00  LDD0445  [2]
STPyne
 Probe Info  		K820(10.00)  LDD0277  [3]
IPM
 Probe Info  		C278(0.00); C595(0.00); C689(0.00); C849(0.00)  LDD0241  [4]
OPA-S-S-alkyne
 Probe Info  		K116(0.76); K115(0.76); K820(4.77)  LDD3494  [5]
DBIA
 Probe Info  		C595(4.36)  LDD3380  [6]
AHL-Pu-1
 Probe Info  		C278(2.62)  LDD0171  [7]
EA-probe
 Probe Info  		N.A.  LDD0440  [8]
W1
 Probe Info  		N.A.  LDD0236  [4]
MPP-AC
 Probe Info  		N.A.  LDD0428  [9]
TER-AC
 Probe Info  		N.A.  LDD0426  [9]
TPP-AC
 Probe Info  		N.A.  LDD0427  [9]
PAL-AfBPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe12
 Probe Info  		20.00  LDD0473  [10]
FFF probe13
 Probe Info  		20.00  LDD0475  [10]
FFF probe9
 Probe Info  		20.00  LDD0470  [10]
JN0003
 Probe Info  		20.00  LDD0469  [10]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0026  4SU-RNA+native RNA DM93 C278(2.62)  LDD0171  [7]
 LDCM0175  Ethacrynic acid HeLa N.A.  LDD0440  [8]
 LDCM0022  KB02 A101D C595(2.84)  LDD2250  [6]
 LDCM0023  KB03 A101D C595(6.14)  LDD2667  [6]
 LDCM0024  KB05 OV-90 C595(4.36)  LDD3380  [6]
 LDCM0112  W16 Hep-G2 C595(0.55)  LDD0239  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 15 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Alpha/beta hydrolase domain-containing protein 17C (ABHD17C) ABHD17 family Q6PCB6
COP9 signalosome complex subunit 3 (COPS3) CSN3 family Q9UNS2
Probable ATP-dependent RNA helicase DDX20 (DDX20) DEAD box helicase family Q9UHI6
Histone acetyltransferase KAT5 (KAT5) MYST (SAS/MOZ) family Q92993
Parkinson disease protein 7 (PARK7) Peptidase C56 family Q99497
Ubiquitin thioesterase OTUB1 (OTUB1) Peptidase C65 family Q96FW1
E3 SUMO-protein ligase PIAS1 (PIAS1) PIAS family O75925
Tyrosine-protein kinase Lyn (LYN) Tyr protein kinase family P07948
Ras-related protein Rab-38 (RAB38) Rab family P57729
Thioredoxin (TXN) Thioredoxin family P10599
RING finger protein 112 (RNF112) GB1/RHD3 GTPase family Q9ULX5
GTPase Era, mitochondrial (ERAL1) Era GTPase family O75616
E3 ubiquitin-protein ligase CHIP (STUB1) . Q9UNE7
E3 ubiquitin-protein ligase LNX (LNX1) . Q8TBB1
E3 ubiquitin-protein ligase RNF183 (RNF183) . Q96D59
Transporter and channel
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
ATPase inhibitor, mitochondrial (ATP5IF1) ATPase inhibitor family Q9UII2
Protein S100-B (S100B) S-100 family P04271
Syntaxin-19 (STX19) Syntaxin family Q8N4C7
Transcription factor
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein Hox-C4 (HOXC4) Antp homeobox family P09017
Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) . Q9H147
Forkhead box protein R1 (FOXR1) . Q6PIV2
LIM/homeobox protein Lhx6 (LHX6) . Q9UPM6
Myeloid cell nuclear differentiation antigen (MNDA) . P41218
Twist-related protein 2 (TWIST2) . Q8WVJ9
Zinc finger protein 366 (ZNF366) . Q8N895
GPCR
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Frizzled-4 (FZD4) G-protein coupled receptor Fz/Smo family Q9ULV1
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Granulocyte-macrophage colony-stimulating factor (CSF2) GM-CSF family P04141
Other
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Catenin beta-1 (CTNNB1) Beta-catenin family P35222
Protein BRICK1 (BRK1) BRK1 family Q8WUW1
Cytoplasmic FMR1-interacting protein 1 (CYFIP1) CYFIP family Q7L576
Histone H2A.Z (H2AZ1) Histone H2A family P0C0S5
Histone H3.1 (H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12) Histone H3 family P68431
Keratin-associated protein 10-7 (KRTAP10-7) KRTAP type 10 family P60409
Keratin-associated protein 8-1 (KRTAP8-1) KRTAP type 8 family Q8IUC2
MORF4 family-associated protein 1 (MRFAP1) MORF4 family-associated protein family Q9Y605
Vacuolar protein sorting-associated protein 33A (VPS33A) STXBP/unc-18/SEC1 family Q96AX1
Syntaxin-11 (STX11) Syntaxin family O75558
U3 small nucleolar RNA-associated protein 14 homolog A (UTP14A) UTP14 family Q9BVJ6
C-type lectin domain family 2 member B (CLEC2B) . Q92478
Protein MGARP (MGARP) . Q8TDB4
Spermatogenesis-associated protein 12 (SPATA12) . Q7Z6I5

The Drug(s) Related To This Target

Approved
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Becaplermin BiotechDrug DB00102
Ocriplasmin BiotechDrug DB08888
Bacitracin Small molecular drug DB00626
Cisplatin Small molecular drug DB00515
Copper . DB09130
Silver . DB12965
Zinc . DB01593
Zinc Acetate . DB14487
Zinc Chloride . DB14533
Zinc Sulfate Unspecified Form . DB14548

References

1 Labeling Preferences of Diazirines with Protein Biomolecules. J Am Chem Soc. 2021 May 5;143(17):6691-6700. doi: 10.1021/jacs.1c02509. Epub 2021 Apr 20.
Mass spectrometry data entry: PXD025140
2 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
3 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
4 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
5 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
6 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
7 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
8 Chemoproteomic Profiling Reveals Ethacrynic Acid Targets Adenine Nucleotide Translocases to Impair Mitochondrial Function. Mol Pharm. 2018 Jun 4;15(6):2413-2422. doi: 10.1021/acs.molpharmaceut.8b00250. Epub 2018 May 15.
9 Differently Tagged Probes for Protein Profiling of Mitochondria. Chembiochem. 2019 May 2;20(9):1155-1160. doi: 10.1002/cbic.201800735. Epub 2019 Mar 26.
10 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.