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Protein

Piwi-like protein 1

Gene

Piwil1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endoribonuclease that plays a central role in postnatal germ cells by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:11578866, PubMed:22121019, PubMed:21237665). 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 governs the methylation and subsequent repression of transposons (PubMed:11578866, PubMed:22121019, PubMed:21237665). Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:11578866, PubMed:22121019, PubMed:21237665). Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias) (PubMed:24757166). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle (PubMed:22121019). Acts as an endoribonuclease that cleaves transposon messenger RNAs (PubMed:22121019). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (PubMed:16938833). Probable component of some RISC complex, which mediates RNA cleavage and translational silencing (PubMed:16938833). Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability (PubMed:16787948). Required to sequester RNF8 in the cytoplasm until late spermatogenesis; RNF8 being released upon ubiquitination and degradation of PIWIL1 (PubMed:28552346).7 Publications

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei382Required for binding 2'-O-methylated 3'-end of piRNAs1
Active sitei6331 Publication1
Active sitei671By similarity1
Active sitei703By similarity1
Active sitei837By similarity1

GO - Molecular functioni

  • endoribonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • mRNA binding Source: UniProtKB
  • piRNA binding Source: UniProtKB
  • protein kinase binding Source: MGI
  • single-stranded RNA binding Source: MGI

GO - Biological processi

  • gene silencing by RNA Source: UniProtKB
  • meiotic cell cycle Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of transposition Source: UniProtKB
  • piRNA metabolic process Source: UniProtKB
  • regulation of translation Source: UniProtKB
  • spermatid development Source: UniProtKB
  • spermatogenesis Source: UniProtKB
  • spermatogenesis, exchange of chromosomal proteins Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 1 (EC:3.1.26.-1 Publication)
Gene namesi
Name:Piwil1
Synonyms:Miwi1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1928897. Piwil1.

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 display spermatogenic arrest at the beginning of the round spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis; mRNAs of FHL5/activator of CREM and CREM target genes are down-regulated in testes. Female are fertile but male are completely sterile, no sperm is found in the epididimus. Chromatoid bodies from round spermatids are not fully compacted and remain as a diffuse chromatoid material.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi218 – 221RRLL → ARLA: Does not affect piRNA-binding but abolishes ubiquitination by the APC/C. Causes male sterility. 2 Publications4
Mutagenesisi330 – 335KSTFKK → ASTFAA: Abolishes ubiquitination by the APC/C. 1 Publication6
Mutagenesisi343F → A: Impairs binding to 2'-O-methylated 3'-end of piRNAs. 1 Publication1
Mutagenesisi346 – 347YY → AA: Abolishes piRNA-binding and ubiquitination by the APC/C. 1 Publication2
Mutagenesisi382M → A: Impairs binding to 2'-O-methylated 3'-end of piRNAs. 1 Publication1
Mutagenesisi633D → A in DAH mutant; causes male infertility due to derepression of LINE1 retrotransposons transcripts. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002345681 – 862Piwi-like protein 1Add BLAST862

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14Omega-N-methylarginine; by PRMT5; alternate1 Publication1
Modified residuei14Symmetric dimethylarginine; by PRMT5; alternate1 Publication1
Modified residuei49Omega-N-methylarginine; by PRMT51 Publication1
Modified residuei53Omega-N-methylarginine; alternate1 Publication1
Modified residuei53Symmetric dimethylarginine; alternate1 Publication1
Modified residuei371Omega-N-methylarginine; by PRMT51 Publication1

Post-translational modificationi

Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in late spermatids, leading to its degradation (PubMed:23328397). Ubiquitination only takes place following piRNA-binding in adult testis (PubMed:23328397). Ubiquitination and degradation in late spermatogenesis by APC/C is probably required to release RNF8 from the cytoplasm and promote histone to protamine exchange by RNF8 (PubMed:28552346).2 Publications
Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein (TDRD1, TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9) and subsequent localization to the meiotic nuage, also named P granule.5 Publications

Keywords - PTMi

Methylation, Ubl conjugation

Proteomic databases

PaxDbiQ9JMB7.
PeptideAtlasiQ9JMB7.
PRIDEiQ9JMB7.

PTM databases

iPTMnetiQ9JMB7.
PhosphoSitePlusiQ9JMB7.

Expressioni

Tissue specificityi

Expressed in brain. Expressed in testis, specifically in spermatocytes (at protein level). Only detected in germ lineage cells of adult testis. Expressed in male gonads 2 weeks after birth at the initiation of spermatogenesis, but not expressed in female gonads.4 Publications

Inductioni

Expression is activated by MYBL1/A-MYB.1 Publication

Gene expression databases

BgeeiENSMUSG00000029423.
CleanExiMM_PIWIL1.
ExpressionAtlasiQ9JMB7. baseline and differential.
GenevisibleiQ9JMB7. MM.

Interactioni

Subunit structurei

Interacts (via Piwi domain) with DICER1, suggesting that it forms ribonucleoprotein RISC complexes; this interaction is regulated by HSP90AB1 activity (PubMed:16938833). Interacts with MAEL, KIF17, PABPC1, PRMT5 and WDR77 (PubMed:16787948, PubMed:16787967, PubMed:19020299, PubMed:19584108). Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9 (PubMed:19584108, PubMed:19918066, PubMed:19926723, PubMed:23714778). Interacts with CLOCK (PubMed:22900038). Interacts with MOV10L1 (PubMed:20534472). Interacts with ANAPC10; interaction oly takes place following piRNA-binding (PubMed:23328397). Interacts with RNF8; leading to sequester RNF8 in the cytoplasm (PubMed:28552346).12 Publications

GO - Molecular functioni

  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi208311. 1 interactor.
DIPiDIP-59456N.
IntActiQ9JMB7. 3 interactors.
STRINGi10090.ENSMUSP00000083222.

Structurei

Secondary structure

1862
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi280 – 290Combined sources11
Helixi293 – 304Combined sources12
Beta strandi308 – 311Combined sources4
Turni312 – 315Combined sources4
Beta strandi316 – 319Combined sources4
Beta strandi322 – 324Combined sources3
Beta strandi335 – 338Combined sources4
Helixi343 – 348Combined sources6
Beta strandi358 – 360Combined sources3
Beta strandi362 – 365Combined sources4
Beta strandi381 – 383Combined sources3
Helixi385 – 387Combined sources3
Beta strandi388 – 390Combined sources3
Beta strandi492 – 494Combined sources3
Beta strandi498 – 502Combined sources5
Helixi503 – 505Combined sources3
Helixi506 – 519Combined sources14
Helixi521 – 523Combined sources3
Beta strandi525 – 527Combined sources3
Beta strandi531 – 535Combined sources5
Helixi539 – 549Combined sources11
Beta strandi557 – 563Combined sources7
Helixi566 – 579Combined sources14
Beta strandi584 – 588Combined sources5
Helixi589 – 592Combined sources4
Helixi595 – 608Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XFMNMR-A276-425[»]
4P1ZX-ray2.30A/B/C/D485-612[»]
ProteinModelPortaliQ9JMB7.
SMRiQ9JMB7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini278 – 392PAZPROSITE-ProRule annotationAdd BLAST115
Domaini556 – 848PiwiPROSITE-ProRule annotationAdd BLAST293

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni317 – 319Required for binding 2'-O-methylated 3'-end of piRNAs1 Publication3
Regioni480 – 616MID region1 PublicationAdd BLAST137

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi218 – 225D-box1 Publication8

Domaini

The D-box (destruction box) acts as a recognition signal for association with the APC/C complex, ubiquitination and degradation (PubMed:23328397).1 Publication
The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs (PubMed:21237665). The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias) (PubMed:24757166).2 Publications

Sequence similaritiesi

Belongs to the argonaute family. Piwi subfamily.Curated

Phylogenomic databases

eggNOGiKOG1042. Eukaryota.
ENOG410XNRH. LUCA.
GeneTreeiENSGT00760000119148.
HOGENOMiHOG000254789.
HOVERGENiHBG049411.
InParanoidiQ9JMB7.
KOiK02156.
OMAiPGYIQPR.
OrthoDBiEOG091G020J.
PhylomeDBiQ9JMB7.
TreeFamiTF354206.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiView protein in InterPro
IPR014811. ArgoL1.
IPR031320. GAGE.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR031326. PIWIL1.
IPR012337. RNaseH-like_dom.
PANTHERiPTHR22891:SF70. PTHR22891:SF70. 1 hit.
PfamiView protein in Pfam
PF08699. ArgoL1. 1 hit.
PF05831. GAGE. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
SMARTiView protein in SMART
SM01379. GAGE. 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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9JMB7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTGRARARAR GRARGQETVQ HVGAAASQQP GYIPPRPQQS PTEGDLVGRG
60 70 80 90 100
RQRGMVVGAT SKSQELQISA GFQELSLAER GGRRRDFHDL GVNTRQNLDH
110 120 130 140 150
VKESKTGSSG IIVKLSTNHF RLTSRPQWAL YQYHIDYNPL MEARRLRSAL
160 170 180 190 200
LFQHEDLIGR CHAFDGTILF LPKRLQHKVT EVFSQTRNGE HVRITITLTN
210 220 230 240 250
ELPPTSPTCL QFYNIIFRRL LKIMNLQQIG RNYYNPSDPI DIPNHRLVIW
260 270 280 290 300
PGFTTSILQY ENNIMLCTDV SHKVLRSETV LDFMFNLYQQ TEEHKFQEQV
310 320 330 340 350
SKELIGLIVL TKYNNKTYRV DDIDWDQNPK STFKKADGSE VSFLEYYRKQ
360 370 380 390 400
YNQEITDLKQ PVLVSQPKRR RGPGGTLPGP AMLIPELCYL TGLTDKMRND
410 420 430 440 450
FNVMKDLAVH TRLTPEQRQR EVGRLIDYIH KDDNVQRELR DWGLSFDSNL
460 470 480 490 500
LSFSGRILQS EKIHQGGKTF DYNPQFADWS KETRGAPLIS VKPLDNWLLI
510 520 530 540 550
YTRRNYEAAN SLIQNLFKVT PAMGIQMKKA IMIEVDDRTE AYLRALQQKV
560 570 580 590 600
TSDTQIVVCL LSSNRKDKYD AIKKYLCTDC PTPSQCVVAR TLGKQQTVMA
610 620 630 640 650
IATKIALQMN CKMGGELWRV DMPLKLAMIV GIDCYHDTTA GRRSIAGFVA
660 670 680 690 700
SINEGMTRWF SRCVFQDRGQ ELVDGLKVCL QAALRAWSGC NEYMPSRVIV
710 720 730 740 750
YRDGVGDGQL KTLVNYEVPQ FLDCLKSVGR GYNPRLTVIV VKKRVNARFF
760 770 780 790 800
AQSGGRLQNP LPGTVIDVEV TRPEWYDFFI VSQAVRSGSV SPTHYNVIYD
810 820 830 840 850
SSGLKPDHIQ RLTYKLCHVY YNWPGVIRVP APCQYAHKLA FLVGQSIHRE
860
PNLSLSNRLY YL
Length:862
Mass (Da):98,574
Last modified:October 1, 2000 - v1
Checksum:i45588D13284CCC4C
GO
Isoform 2 (identifier: Q9JMB7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     825-862: GVIRVPAPCQYAHKLAFLVGQSIHREPNLSLSNRLYYL → VSVLLWTTYPG

Note: No experimental confirmation available.
Show »
Length:835
Mass (Da):95,484
Checksum:i3F96A55A0DEE610F
GO

Sequence cautioni

The sequence AAH66846 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti374G → S in AAH66846 (PubMed:15489334).Curated1
Sequence conflicti468K → R in AAH66846 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_036663825 – 862GVIRV…RLYYL → VSVLLWTTYPG in isoform 2. 1 PublicationAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB032604 mRNA. Translation: BAA93705.1.
AF438405 mRNA. Translation: AAL31014.1.
EF196092 mRNA. Translation: ABM69181.1.
BC066846 mRNA. Translation: AAH66846.1. Sequence problems.
BC129857 mRNA. Translation: AAI29858.1.
BC129858 mRNA. Translation: AAI29859.1.
CCDSiCCDS19690.1. [Q9JMB7-1]
RefSeqiNP_067286.1. NM_021311.3. [Q9JMB7-1]
XP_006504381.1. XM_006504318.1. [Q9JMB7-1]
UniGeneiMm.272720.

Genome annotation databases

EnsembliENSMUST00000086056; ENSMUSP00000083222; ENSMUSG00000029423. [Q9JMB7-1]
ENSMUST00000195959; ENSMUSP00000142386; ENSMUSG00000029423. [Q9JMB7-2]
GeneIDi57749.
KEGGimmu:57749.
UCSCiuc008zsi.1. mouse. [Q9JMB7-1]
uc008zsj.1. mouse. [Q9JMB7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPIWL1_MOUSE
AccessioniPrimary (citable) accession number: Q9JMB7
Secondary accession number(s): A1L324, A1L325, Q6NXX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: October 1, 2000
Last modified: September 27, 2017
This is version 119 of the entry and version 1 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families