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Protein

Piwi-like protein 2

Gene

Piwil2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). 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 (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). 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 (PubMed:22020280, PubMed:23706823, PubMed:26669262). 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 (PubMed:28633017). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (PubMed:18381894, PubMed:18922463, PubMed:26669262). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (PubMed:19114715). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (PubMed:16261612).11 Publications

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei743By similarity1
Active sitei781By similarity1
Active sitei813By similarity1
Active sitei946By similarity1

GO - Molecular functioni

  • endoribonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • mRNA binding Source: UniProtKB
  • piRNA binding Source: UniProtKB

GO - Biological processi

  • DNA methylation involved in gamete generation Source: UniProtKB
  • gene silencing by RNA Source: UniProtKB
  • germ-line stem cell population maintenance Source: UniProtKB
  • meiotic cell cycle Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of transposition Source: UniProtKB
  • oogenesis Source: UniProtKB
  • piRNA biosynthetic process Source: UniProtKB
  • piRNA metabolic process Source: UniProtKB
  • positive regulation of histone H3-K14 acetylation Source: CACAO
  • positive regulation of histone H3-K9 acetylation Source: CACAO
  • positive regulation of meiosis I Source: MGI
  • positive regulation of translation Source: UniProtKB
  • RNA 5'-end processing Source: UniProtKB
  • spermatogenesis Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein, Endonuclease, Hydrolase, Nuclease, RNA-binding
Biological processDifferentiation, Meiosis, Oogenesis, RNA-mediated gene silencing, Spermatogenesis, Translation regulation
LigandMetal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 2Curated (EC:3.1.26.-3 Publications)
Gene namesi
Name:Piwil2Imported
Synonyms:Mili2 Publications
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1930036 Piwil2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice exhibit blocked spermatogenesis at the early prophase of the first meiosis due to transposable elements derepression, and apoptosis occurs subsequently. Female mice are fertile, while male are sterile.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi9R → K: Abolishes interaction with TDRD1; when associated with K-39; K-45 and K-74. 1 Publication1
Mutagenesisi39R → K: Abolishes interaction with TDRD1; when associated with K-9; K-45 and K-74. 1 Publication1
Mutagenesisi45R → K: Abolishes interaction with TDRD1; when associated with K-9; K-39 and K-74. 1 Publication1
Mutagenesisi74R → K: Abolishes interaction with TDRD1; when associated with K-9; K-39 and K-45. 1 Publication1
Mutagenesisi813D → A in DAH mutant; leads to arrest in meiotic prophase due to a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA-bound within PIWIL4. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002345701 – 971Piwi-like protein 2Add BLAST971

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45Symmetric dimethylarginine2 Publications1
Modified residuei74Omega-N-methylarginine; by PRMT5; alternate4 Publications1
Modified residuei74Symmetric dimethylarginine; by PRMT5; alternate4 Publications1
Modified residuei83Omega-N-methylarginine; alternate1 Publication1
Modified residuei83Symmetric dimethylarginine; alternate1 Publication1
Modified residuei95Omega-N-methylarginine; by PRMT5; alternate2 Publications1
Modified residuei95Symmetric dimethylarginine; alternate2 Publications1
Modified residuei100Omega-N-methylarginine; alternate2 Publications1
Modified residuei100Symmetric dimethylarginine; by PRMT5; alternate2 Publications1
Modified residuei144Symmetric dimethylarginine1 Publication1
Modified residuei156Symmetric dimethylarginine1 Publication1
Modified residuei163Symmetric dimethylarginine; by PRMT52 Publications1
Modified residuei549Symmetric dimethylarginine; by PRMT51 Publication1

Post-translational modificationi

Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein TDRD1 and subsequent localization to the meiotic nuage, also named P granule.5 Publications

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiQ8CDG1
PRIDEiQ8CDG1

PTM databases

iPTMnetiQ8CDG1
PhosphoSitePlusiQ8CDG1

Expressioni

Tissue specificityi

Expressed in adult testis, specifically in spermatocytes and in spermatogonia (PubMed:11279525, PubMed:11578866, PubMed:12906857, PubMed:18404146, PubMed:18922463, PubMed:19114715, PubMed:19377467). Only detected in primordial germ cells of both sexes. Widely expressed in tumors. Also present at early stages of oocyte growth. Expressed in brain (at protein level). Present in the mitotic spermatogonia (PubMed:23706823). Not detected in the first stages of meiosis (preleptotene and leptotene) (PubMed:23706823). Detected at the late zygotene stage and increases throughout pachytene, declining from this stage onward until expression stops at the early round spermatid stage (at protein level) (PubMed:23706823).8 Publications

Developmental stagei

Expressed from E12.5 until adult in male gonads. In female gonads, detected since E12.5, then begins to cease after birth and disappears until the development of adult ovary.1 Publication

Gene expression databases

BgeeiENSMUSG00000033644
CleanExiMM_PIWIL2
GenevisibleiQ8CDG1 MM

Interactioni

Subunit structurei

Interacts with DDX4, MAEL, EIF3A, EIF4E, EIF4G, PRMT5 and WDR77. Associates with EIF4E- and EIF4G-containing m7G cap-binding complexes. Interacts (when methylated on arginine residues) with TDRD1 and TDRKH/TDRD2. Interacts with TDRD12 (PubMed:24067652). Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs (PubMed:26669262). Interacts with MOV10L1 (PubMed:20534472, PubMed:20547853). Interacts with GPAT2 (PubMed:23611983). Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886).14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Tdrd1Q99MV16EBI-8573412,EBI-8573364

Protein-protein interaction databases

BioGridi208309, 2 interactors
DIPiDIP-48522N
IntActiQ8CDG1, 4 interactors
MINTiQ8CDG1
STRINGi10090.ENSMUSP00000047385

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4B9WX-ray2.10P/S38-50[»]
ProteinModelPortaliQ8CDG1
SMRiQ8CDG1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini386 – 494PAZPROSITE-ProRule annotationAdd BLAST109
Domaini666 – 957PiwiPROSITE-ProRule annotationAdd BLAST292

Sequence similaritiesi

Belongs to the argonaute family. Piwi subfamily.Curated

Phylogenomic databases

eggNOGiKOG1042 Eukaryota
ENOG410XNRH LUCA
GeneTreeiENSGT00760000119148
HOGENOMiHOG000254789
HOVERGENiHBG049411
InParanoidiQ8CDG1
KOiK02156
OMAiHHSALEC
OrthoDBiEOG091G020J
PhylomeDBiQ8CDG1
TreeFamiTF354206

Family and domain databases

Gene3Di3.30.420.10, 1 hit
InterProiView protein in InterPro
IPR014811 ArgoL1
IPR003100 PAZ_dom
IPR036085 PAZ_dom_sf
IPR003165 Piwi
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
PfamiView protein in Pfam
PF08699 ArgoL1, 1 hit
PF02170 PAZ, 1 hit
PF02171 Piwi, 1 hit
SMARTiView protein in SMART
SM01163 DUF1785, 1 hit
SM00949 PAZ, 1 hit
SM00950 Piwi, 1 hit
SUPFAMiSSF101690 SSF101690, 1 hit
SSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS50821 PAZ, 1 hit
PS50822 PIWI, 1 hit

Sequencei

Sequence statusi: Complete.

Q8CDG1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPVRPLFRG PTPVHPSQCV RMPGCWPQAP RPLEPAWGRA GPAGRGLVFR
60 70 80 90 100
KPEDSSPPLQ PVQKDSVGLV SMFRGMGLDT AFRPPSKREV PPLGRGVLGR
110 120 130 140 150
GLSANMVRKD REEPRSSLPD PSVLAAGDSK LAEASVGWSR MLGRGSSEVS
160 170 180 190 200
LLPLGRAASS IGRGMDKPPS AFGLTARDPP RLPQPPALSP TSLHSADPPP
210 220 230 240 250
VLTMERKEKE LLVKQGSKGT PQSLGLNLIK IQCHNEAVYQ YHVTFSPSVE
260 270 280 290 300
CKSMRFGMLK DHQSVTGNVT AFDGSILYLP VKLQQVVELK SQRKTDDAEI
310 320 330 340 350
SIKIQLTKIL EPCSDLCIPF YNVVFRRVMK LLDMKLVGRN FYDPTSAMVL
360 370 380 390 400
QQHRLQIWPG YAASIRRTDG GLFLLADVSH KVIRNDSVLD VMHAIYQQNK
410 420 430 440 450
EHFQDECSKL LVGSIVITRY NNRTYRIDDV DWNKTPKDSF VMSDGKEITF
460 470 480 490 500
LEYYSKNYGI TVKEDDQPLL IHRPSERQNN HGMLLKGEIL LLPELSFMTG
510 520 530 540 550
IPEKMKKDFR AMKDLTQQIN LSPKQHHGAL ECLLQRISQN ETASNELTRW
560 570 580 590 600
GLSLHKDVHK IEGRLLPMER INLRNTSFVT SEDLNWVKEV TRDASILTIP
610 620 630 640 650
MHFWALFYPK RAMDQARELV NMLEKIAGPI GMRISPPAWV ELKDDRIETY
660 670 680 690 700
IRTIQSLLGV EGKIQMVVCI IMGTRDDLYG AIKKLCCVQS PVPSQVINVR
710 720 730 740 750
TIGQPTRLRS VAQKILLQMN CKLGGELWGV DIPLKQLMVI GMDVYHDPSR
760 770 780 790 800
GMRSVVGFVA SINLTLTKWY SRVVFQMPHQ EIVDSLKLCL VGSLKKYYEV
810 820 830 840 850
NHCLPEKIVV YRDGVSDGQL KTVANYEIPQ LQKCFEAFDN YHPKMVVFVV
860 870 880 890 900
QKKISTNLYL AAPDHFVTPS PGTVVDHTIT SCEWVDFYLL AHHVRQGCGI
910 920 930 940 950
PTHYICVLNT ANLSPDHMQR LTFKLCHMYW NWPGTIRVPA PCKYAHKLAF
960 970
LSGQILHHEP AIQLCGNLFF L
Length:971
Mass (Da):109,488
Last modified:May 16, 2006 - v2
Checksum:i01E143C6513310FB
GO

Sequence cautioni

The sequence AAK31965 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti517Q → E in BAE37436 (PubMed:16141072).Curated1
Sequence conflicti542T → A in BAC26791 (PubMed:16141072).Curated1
Sequence conflicti583D → G in AAK31965 (PubMed:11279525).Curated1
Sequence conflicti634I → T in AAK31965 (PubMed:11279525).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB032605 mRNA Translation: BAA93706.1
AK030116 mRNA Translation: BAC26791.1
AK163647 mRNA Translation: BAE37436.1
CH466535 Genomic DNA Translation: EDL35904.1
BC138444 mRNA Translation: AAI38445.1
BC145717 mRNA Translation: AAI45718.1
AF285586 mRNA Translation: AAK31965.1 Different initiation.
CCDSiCCDS27252.1
RefSeqiNP_067283.1, NM_021308.1
XP_006519392.1, XM_006519329.3
UniGeneiMm.85253

Genome annotation databases

EnsembliENSMUST00000048129; ENSMUSP00000047385; ENSMUSG00000033644
GeneIDi57746
KEGGimmu:57746
UCSCiuc007unx.1 mouse

Similar proteinsi

Entry informationi

Entry nameiPIWL2_MOUSE
AccessioniPrimary (citable) accession number: Q8CDG1
Secondary accession number(s): A6H617
, Q3TQE8, Q99MV6, Q9JMB6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: March 28, 2018
This is version 120 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health