General Information of Target

Target ID LDTP09372
Target Name Piwi-like protein 2 (PIWIL2)
Gene Name PIWIL2
Gene ID 55124
Synonyms
HILI; Piwi-like protein 2; EC 3.1.26.-; Cancer/testis antigen 80; CT80
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MDPFRPSFRGQSPIHPSQCQAVRMPGCWPQASKPLDPALGRGAPAGRGHVFGKPEEPSTQ
RGPAQRESVGLVSMFRGLGIETVSKTPLKREMLPSGRGILGRGLSANLVRKDREELSPTF
WDPKVLAAGDSKMAETSVGWSRTLGRGSSDASLLPLGRAAGGISREVDKPPCTFSTPSRG
PPQLSSPPALPQSPLHSPDRPLVLTVEHKEKELIVKQGSKGTPQSLGLNLVKIQCHNEAV
YQYHVTFSPNVECKSMRFGMLKDHQAVTGNVTAFDGSILYLPVKLQQVLELKSQRKTDSA
EISIKIQMTKILEPCSDLCIPFYNVVFRRVMKLLDMKLVGRNFYDPTSAMVLQQHRLQIW
PGYAASIRRTDGGLFLLADVSHKVIRNDCVLDVMHAIYQQNKEHFQDECTKLLVGNIVIT
RYNNRTYRIDDVDWNKTPKDSFTMSDGKEITFLEYYSKNYGITVKEEDQPLLIHRPSERQ
DNHGMLLKGEILLLPELSFMTGIPEKMKKDFRAMKDLAQQINLSPKQHHSALECLLQRIA
KNEAATNELMRWGLRLQKDVHKIEGRVLPMERINLKNTSFITSQELNWVKEVTRDPSILT
IPMHFWALFYPKRAMDQARELVNMLEKIAGPIGMRMSPPAWVELKDDRIETYVRTIQSTL
GAEGKIQMVVCIIMGPRDDLYGAIKKLCCVQSPVPSQVVNVRTIGQPTRLRSVAQKILLQ
INCKLGGELWGVDIPLKQLMVIGMDVYHDPSRGMRSVVGFVASINLTLTKWYSRVVFQMP
HQEIVDSLKLCLVGSLKKFYEVNHCLPEKIVVYRDGVSDGQLKTVANYEIPQLQKCFEAF
ENYQPKMVVFVVQKKISTNLYLAAPQNFVTPTPGTVVDHTITSCEWVDFYLLAHHVRQGC
GIPTHYVCVLNTANLSPDHMQRLTFKLCHMYWNWPGTIRVPAPCKYAHKLAFLSGHILHH
EPAIQLCENLFFL
Target Bioclass
Enzyme
Family
Argonaute family, Piwi subfamily
Subcellular location
Cytoplasm
Function
Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' PIWIL4. PIWIL2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded. Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8. When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of proliferation in tumors. Represses circadian rhythms by promoting the stability and activity of core clock components BMAL1 and CLOCK by inhibiting GSK3B-mediated phosphorylation and ubiquitination-dependent degradation of these proteins.
Uniprot ID
Q8TC59
Ensemble ID
ENST00000356766.11
HGNC ID
HGNC:17644

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 Deletion: p.G10AfsTer79 .
CCK81 SNV: p.W771R .
GB2 SNV: p.E505Q .
HCT15 SNV: p.M1? .
HGC27 SNV: p.R341I .
IGROV1 SNV: p.F442V .
JURKAT SNV: p.T501I .
LN229 SNV: p.A45E .
LOXIMVI SNV: p.G816R .
MFE319 SNV: p.M507T .
OVKATE SNV: p.E212Q .
SG231 SNV: p.Q399H .
SW480 SNV: p.K798M .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C723(1.99)  LDD3423  [1]
Acrolein
 Probe Info 
N.A.  LDD0217  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A673 C723(1.36)  LDD2261  [1]
 LDCM0023  KB03 A673 C723(1.56)  LDD2678  [1]
 LDCM0024  KB05 SK-ES1 C723(1.99)  LDD3423  [1]
 LDCM0109  NEM HeLa N.A.  LDD0230  [2]

References

1 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
2 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.