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Protein

Piwi-like protein 2

Gene

PIWIL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females. 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. Directly binds 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. Associates with primary piRNAs in the cytoplasm and is required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense. The piRNA process acts upstream of known mediators of DNA methylation. Participates in a piRNA amplification loop. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Indirectly modulate expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (By similarity). Inhibits tumor cell growth when repressed. When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of proliferation in tumors (PubMed:16377660).By similarity1 Publication

GO - Molecular functioni

  • mRNA binding Source: Ensembl
  • piRNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Meiosis, Oogenesis, RNA-mediated gene silencing, Spermatogenesis, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:G66-33700-MONOMER.
ReactomeiR-HSA-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 2
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

HGNCiHGNC:17644. PIWIL2.

Subcellular locationi

  • Cytoplasm By similarity

  • Note: Present in chromatoid body. Probable component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

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 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.

PTM databases

iPTMnetiQ8TC59.
PhosphoSitePlusiQ8TC59.

Expressioni

Tissue specificityi

Expressed in adult testis and in most tumors.1 Publication

Gene expression databases

BgeeiENSG00000197181.
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.By similarity

Protein-protein interaction databases

BioGridi120431. 2 interactors.
IntActiQ8TC59. 9 interactors.
STRINGi9606.ENSP00000349208.

Structurei

Secondary structure

1973
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi390 – 413Combined sources24
Beta strandi417 – 420Combined sources4
Turni421 – 423Combined sources3
Beta strandi426 – 428Combined sources3
Beta strandi431 – 433Combined sources3
Beta strandi440 – 443Combined sources4
Beta strandi449 – 451Combined sources3
Helixi452 – 460Combined sources9
Beta strandi471 – 474Combined sources4
Beta strandi477 – 480Combined sources4
Beta strandi482 – 485Combined sources4
Beta strandi491 – 493Combined sources3
Helixi495 – 497Combined sources3

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...

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
Contains 1 PAZ domain.PROSITE-ProRule annotation
Contains 1 Piwi domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1042. Eukaryota.
ENOG410XNRH. LUCA.
GeneTreeiENSGT00760000119148.
HOVERGENiHBG049411.
InParanoidiQ8TC59.
KOiK02156.
OMAiDVMHAIY.
OrthoDBiEOG091G020J.
PhylomeDBiQ8TC59.
TreeFamiTF354206.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR014811. ArgoL1.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF08699. ArgoL1. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTiSM01163. DUF1785. 1 hit.
SM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMiSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]

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.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.
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

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.
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. 2 interactors.
IntActiQ8TC59. 9 interactors.
STRINGi9606.ENSP00000349208.

PTM databases

iPTMnetiQ8TC59.
PhosphoSitePlusiQ8TC59.

Polymorphism and mutation databases

BioMutaiPIWIL2.
DMDMi74730558.

Proteomic databases

PaxDbiQ8TC59.
PeptideAtlasiQ8TC59.
PRIDEiQ8TC59.

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.
GeneCardsiPIWIL2.
HGNCiHGNC:17644. PIWIL2.
MIMi610312. gene.
neXtProtiNX_Q8TC59.
OpenTargetsiENSG00000197181.
PharmGKBiPA38461.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1042. Eukaryota.
ENOG410XNRH. LUCA.
GeneTreeiENSGT00760000119148.
HOVERGENiHBG049411.
InParanoidiQ8TC59.
KOiK02156.
OMAiDVMHAIY.
OrthoDBiEOG091G020J.
PhylomeDBiQ8TC59.
TreeFamiTF354206.

Enzyme and pathway databases

BioCyciZFISH:G66-33700-MONOMER.
ReactomeiR-HSA-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Miscellaneous databases

ChiTaRSiPIWIL2. human.
GenomeRNAii55124.
PROiQ8TC59.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197181.
CleanExiHS_PIWIL2.
ExpressionAtlasiQ8TC59. baseline and differential.
GenevisibleiQ8TC59. HS.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR014811. ArgoL1.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF08699. ArgoL1. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTiSM01163. DUF1785. 1 hit.
SM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMiSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPIWL2_HUMAN
AccessioniPrimary (citable) accession number: Q8TC59
Secondary accession number(s): A8K4S3
, A8K8S5, B0AZN9, B0AZP2, B4DR22, E7ECA4, Q96SW6, Q9NW28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: June 1, 2002
Last modified: November 30, 2016
This is version 125 of the entry and version 1 of the sequence. [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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.