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Protein

Piwi-like protein 2

Gene

PIWIL2

Organism
Homo sapiens (Human)
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 (By similarity). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (By similarity). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (By similarity). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (By similarity). When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of proliferation in tumors (PubMed:16377660).By similarity1 Publication

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei745By similarity1
Active sitei783By similarity1
Active sitei815By similarity1
Active sitei948By similarity1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-5601884 PIWI-interacting RNA (piRNA) biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 2 (EC:3.1.26.-By similarity)
Alternative name(s):
Cancer/testis antigen 80
Short name:
CT80
Gene namesi
Name:PIWIL2
Synonyms:HILI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000197181.11
HGNCiHGNC:17644 PIWIL2
MIMi610312 gene
neXtProtiNX_Q8TC59

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

Organism-specific databases

DisGeNETi55124
OpenTargetsiENSG00000197181
PharmGKBiPA38461

Polymorphism and mutation databases

BioMutaiPIWIL2
DMDMi74730558

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002345691 – 973Piwi-like protein 2Add BLAST973

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47Symmetric dimethylarginineBy similarity1
Modified residuei76Omega-N-methylarginine; by PRMT5; alternateBy similarity1
Modified residuei76Symmetric dimethylarginine; by PRMT5; alternateBy similarity1
Modified residuei97Omega-N-methylarginine; by PRMT5; alternateBy similarity1
Modified residuei97Symmetric dimethylarginine; alternateBy similarity1
Modified residuei102Omega-N-methylarginine; alternateBy similarity1
Modified residuei102Symmetric dimethylarginine; by PRMT5; alternateBy similarity1
Modified residuei146Symmetric dimethylarginineBy similarity1
Modified residuei158Symmetric dimethylarginineBy similarity1
Modified residuei165Symmetric dimethylarginine; by PRMT5By similarity1
Modified residuei551Symmetric dimethylarginine; by PRMT5By similarity1

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.By similarity

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiQ8TC59
PeptideAtlasiQ8TC59
PRIDEiQ8TC59
ProteomicsDBi74093
74094 [Q8TC59-2]

PTM databases

iPTMnetiQ8TC59
PhosphoSitePlusiQ8TC59

Expressioni

Tissue specificityi

Expressed in adult testis and in most tumors.1 Publication

Gene expression databases

BgeeiENSG00000197181 Expressed in 128 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_PIWIL2
ExpressionAtlasiQ8TC59 baseline and differential
GenevisibleiQ8TC59 HS

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. Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs. Interacts with MOV10L1. Interacts with GPAT2. Interacts with TEX19 (By similarity).By similarity

Protein-protein interaction databases

BioGridi120431, 3 interactors
IntActiQ8TC59, 9 interactors
STRINGi9606.ENSP00000349208

Structurei

Secondary structure

1973
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8TC59
SMRiQ8TC59
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini384 – 496PAZPROSITE-ProRule annotationAdd BLAST113
Domaini668 – 959PiwiPROSITE-ProRule annotationAdd BLAST292

Sequence similaritiesi

Belongs to the argonaute family. Piwi subfamily.Curated

Phylogenomic databases

eggNOGiKOG1042 Eukaryota
ENOG410XNRH LUCA
GeneTreeiENSGT00760000119148
HOVERGENiHBG049411
InParanoidiQ8TC59
KOiK02156
OMAiNKEHFQD
OrthoDBiEOG091G020J
PhylomeDBiQ8TC59
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q8TC59-1) [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
MDPFRPSFRG QSPIHPSQCQ AVRMPGCWPQ ASKPLDPALG RGAPAGRGHV
60 70 80 90 100
FGKPEEPSTQ RGPAQRESVG LVSMFRGLGI ETVSKTPLKR EMLPSGRGIL
110 120 130 140 150
GRGLSANLVR KDREELSPTF WDPKVLAAGD SKMAETSVGW SRTLGRGSSD
160 170 180 190 200
ASLLPLGRAA GGISREVDKP PCTFSTPSRG PPQLSSPPAL PQSPLHSPDR
210 220 230 240 250
PLVLTVEHKE KELIVKQGSK GTPQSLGLNL VKIQCHNEAV YQYHVTFSPN
260 270 280 290 300
VECKSMRFGM LKDHQAVTGN VTAFDGSILY LPVKLQQVLE LKSQRKTDSA
310 320 330 340 350
EISIKIQMTK ILEPCSDLCI PFYNVVFRRV MKLLDMKLVG RNFYDPTSAM
360 370 380 390 400
VLQQHRLQIW PGYAASIRRT DGGLFLLADV SHKVIRNDCV LDVMHAIYQQ
410 420 430 440 450
NKEHFQDECT KLLVGNIVIT RYNNRTYRID DVDWNKTPKD SFTMSDGKEI
460 470 480 490 500
TFLEYYSKNY GITVKEEDQP LLIHRPSERQ DNHGMLLKGE ILLLPELSFM
510 520 530 540 550
TGIPEKMKKD FRAMKDLAQQ INLSPKQHHS ALECLLQRIA KNEAATNELM
560 570 580 590 600
RWGLRLQKDV HKIEGRVLPM ERINLKNTSF ITSQELNWVK EVTRDPSILT
610 620 630 640 650
IPMHFWALFY PKRAMDQARE LVNMLEKIAG PIGMRMSPPA WVELKDDRIE
660 670 680 690 700
TYVRTIQSTL GAEGKIQMVV CIIMGPRDDL YGAIKKLCCV QSPVPSQVVN
710 720 730 740 750
VRTIGQPTRL RSVAQKILLQ INCKLGGELW GVDIPLKQLM VIGMDVYHDP
760 770 780 790 800
SRGMRSVVGF VASINLTLTK WYSRVVFQMP HQEIVDSLKL CLVGSLKKFY
810 820 830 840 850
EVNHCLPEKI VVYRDGVSDG QLKTVANYEI PQLQKCFEAF ENYQPKMVVF
860 870 880 890 900
VVQKKISTNL YLAAPQNFVT PTPGTVVDHT ITSCEWVDFY LLAHHVRQGC
910 920 930 940 950
GIPTHYVCVL NTANLSPDHM QRLTFKLCHM YWNWPGTIRV PAPCKYAHKL
960 970
AFLSGHILHH EPAIQLCENL FFL
Length:973
Mass (Da):109,849
Last modified:June 1, 2002 - v1
Checksum:iC44398136B144CA0
GO
Isoform 2 (identifier: Q8TC59-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     887-922: Missing.

Show »
Length:937
Mass (Da):105,760
Checksum:i5888D266DD32416C
GO

Sequence cautioni

The sequence BAA91558 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55155 differs from that shown. Reason: Erroneous termination at position 421. Translated as Arg.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18Q → R in BAG61134 (PubMed:14702039).Curated1
Sequence conflicti581I → T in BAF98721 (PubMed:14702039).Curated1
Sequence conflicti685K → N in BAA91558 (PubMed:14702039).Curated1
Sequence conflicti720Q → R in BAF98724 (PubMed:14702039).Curated1
Sequence conflicti887V → G in BAF83727 (PubMed:14702039).Curated1
Sequence conflicti961E → G in BAB55155 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_036664887 – 922Missing in isoform 2. 2 PublicationsAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079367 mRNA Translation: BAC81342.1
HQ651229 mRNA Translation: ADV17663.1
AK001213 mRNA Translation: BAA91558.1 Different initiation.
AK027497 mRNA Translation: BAB55155.1 Sequence problems.
AK291038 mRNA Translation: BAF83727.1
AK292440 mRNA Translation: BAF85129.1
AK299068 mRNA Translation: BAG61134.1
AK315830 mRNA Translation: BAF98721.1
AK315833 mRNA Translation: BAF98724.1
BC025995 mRNA Translation: AAH25995.1
BC111751 mRNA Translation: AAI11752.1
CCDSiCCDS6029.1 [Q8TC59-1]
CCDS83261.1 [Q8TC59-2]
RefSeqiNP_001129193.1, NM_001135721.1 [Q8TC59-1]
NP_001317409.1, NM_001330480.1 [Q8TC59-2]
NP_060538.2, NM_018068.3 [Q8TC59-1]
UniGeneiHs.614809

Genome annotation databases

EnsembliENST00000356766; ENSP00000349208; ENSG00000197181 [Q8TC59-1]
ENST00000454009; ENSP00000406956; ENSG00000197181 [Q8TC59-1]
ENST00000521356; ENSP00000428267; ENSG00000197181 [Q8TC59-2]
ENST00000611073; ENSP00000478103; ENSG00000197181 [Q8TC59-2]
GeneIDi55124
KEGGihsa:55124
UCSCiuc011kzf.2 human [Q8TC59-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079367 mRNA Translation: BAC81342.1
HQ651229 mRNA Translation: ADV17663.1
AK001213 mRNA Translation: BAA91558.1 Different initiation.
AK027497 mRNA Translation: BAB55155.1 Sequence problems.
AK291038 mRNA Translation: BAF83727.1
AK292440 mRNA Translation: BAF85129.1
AK299068 mRNA Translation: BAG61134.1
AK315830 mRNA Translation: BAF98721.1
AK315833 mRNA Translation: BAF98724.1
BC025995 mRNA Translation: AAH25995.1
BC111751 mRNA Translation: AAI11752.1
CCDSiCCDS6029.1 [Q8TC59-1]
CCDS83261.1 [Q8TC59-2]
RefSeqiNP_001129193.1, NM_001135721.1 [Q8TC59-1]
NP_001317409.1, NM_001330480.1 [Q8TC59-2]
NP_060538.2, NM_018068.3 [Q8TC59-1]
UniGeneiHs.614809

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3O7XX-ray2.92A/B/C/D387-525[»]
3QIRX-ray2.45A/B/C/D386-533[»]
ProteinModelPortaliQ8TC59
SMRiQ8TC59
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120431, 3 interactors
IntActiQ8TC59, 9 interactors
STRINGi9606.ENSP00000349208

PTM databases

iPTMnetiQ8TC59
PhosphoSitePlusiQ8TC59

Polymorphism and mutation databases

BioMutaiPIWIL2
DMDMi74730558

Proteomic databases

PaxDbiQ8TC59
PeptideAtlasiQ8TC59
PRIDEiQ8TC59
ProteomicsDBi74093
74094 [Q8TC59-2]

Protocols and materials databases

DNASUi55124
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356766; ENSP00000349208; ENSG00000197181 [Q8TC59-1]
ENST00000454009; ENSP00000406956; ENSG00000197181 [Q8TC59-1]
ENST00000521356; ENSP00000428267; ENSG00000197181 [Q8TC59-2]
ENST00000611073; ENSP00000478103; ENSG00000197181 [Q8TC59-2]
GeneIDi55124
KEGGihsa:55124
UCSCiuc011kzf.2 human [Q8TC59-1]

Organism-specific databases

CTDi55124
DisGeNETi55124
EuPathDBiHostDB:ENSG00000197181.11
GeneCardsiPIWIL2
HGNCiHGNC:17644 PIWIL2
MIMi610312 gene
neXtProtiNX_Q8TC59
OpenTargetsiENSG00000197181
PharmGKBiPA38461
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1042 Eukaryota
ENOG410XNRH LUCA
GeneTreeiENSGT00760000119148
HOVERGENiHBG049411
InParanoidiQ8TC59
KOiK02156
OMAiNKEHFQD
OrthoDBiEOG091G020J
PhylomeDBiQ8TC59
TreeFamiTF354206

Enzyme and pathway databases

ReactomeiR-HSA-5601884 PIWI-interacting RNA (piRNA) biogenesis

Miscellaneous databases

ChiTaRSiPIWIL2 human
GenomeRNAii55124
PROiPR:Q8TC59
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197181 Expressed in 128 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_PIWIL2
ExpressionAtlasiQ8TC59 baseline and differential
GenevisibleiQ8TC59 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiPIWL2_HUMAN
AccessioniPrimary (citable) accession number: Q8TC59
Secondary accession number(s): A8K4S3
, A8K8S5, B0AZN9, B0AZP2, B4DR22, E7ECA4, Q96SW6, Q9NW28
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: June 1, 2002
Last modified: November 7, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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