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Protein

Piwi-like protein 1

Gene

PIWIL1

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. 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 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. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability (By similarity). Isoform 3 may be a negative developmental regulator (PubMed:12037681, PubMed:16287078).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei381Required for binding 2'-O-methylated 3'-end of piRNAs1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

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

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125207-MONOMER.
ReactomeiR-HSA-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 1
Gene namesi
Name:PIWIL1
Synonyms:HIWI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:9007. PIWIL1.

Subcellular locationi

  • Cytoplasm By similarity

  • Note: Component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis. Also present in chromatoid body.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi379P → H: Impairs binding to 2'-O-methylated 3'-end of piRNAs; when associated with Y-381. 1 Publication1
Mutagenesisi381M → Y: Impairs binding to 2'-O-methylated 3'-end of piRNAs; when associated with H-379. 1 Publication1

Organism-specific databases

DisGeNETi9271.
OpenTargetsiENSG00000125207.
ENSG00000275051.
PharmGKBiPA33341.

Polymorphism and mutation databases

BioMutaiPIWIL1.
DMDMi74716803.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002345671 – 861Piwi-like protein 1Add BLAST861

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14Omega-N-methylarginine; by PRMT5; alternateBy similarity1
Modified residuei14Symmetric dimethylarginine; by PRMT5; alternateBy similarity1
Modified residuei49Omega-N-methylarginine; by PRMT5By similarity1
Modified residuei53Omega-N-methylarginineBy similarity1
Modified residuei370Omega-N-methylarginine; by PRMT5By similarity1

Post-translational modificationi

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.By similarity

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiQ96J94.
PeptideAtlasiQ96J94.
PRIDEiQ96J94.

PTM databases

iPTMnetiQ96J94.
PhosphoSitePlusiQ96J94.

Expressioni

Tissue specificityi

Expressed in spermatocytes and spermatids. Also detected in prostate cancer (at protein level). Detected in most fetal and adult tissues. Expressed in testes, specifically in germline cells; detected in spermatocytes and spermatids during spermatogenesis. Increased expression in testicular tumors originating from embryonic germ cells with retention of germ cells phenotype. No expression in testicular tumors of somatic origin, such as Sertoli cell and Leydig cell tumors. Overexpressed in gastric cancer cells. Isoform 3 is ubiquitously expressed, and specifically in CD34+ hematopoietic progenitor cells but not in more differentiated cells.4 Publications

Inductioni

Isoform 3 is down-regulated in CD34+ hematopoietic cells during differentiation.1 Publication

Gene expression databases

BgeeiENSG00000125207.
CleanExiHS_PIWIL1.
ExpressionAtlasiQ96J94. baseline and differential.
GenevisibleiQ96J94. HS.

Organism-specific databases

HPAiCAB012217.
HPA018798.

Interactioni

Subunit structurei

Interacts (via Piwi domain) with DICER1, suggesting that it forms ribonucleoprotein RISC complexes; this interaction is regulated by HSP90AB1 activity. Interacts with MAEL, KIF17, PABPC1, PRMT5 and WDR77. Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9. Interacts with CLOCK. Interacts with MOV10L1.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
DICER1Q9UPY32EBI-527417,EBI-395506

Protein-protein interaction databases

BioGridi114690. 7 interactors.
DIPiDIP-33534N.
IntActiQ96J94. 12 interactors.
STRINGi9606.ENSP00000245255.

Structurei

Secondary structure

1861
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi279 – 285Combined sources7
Helixi286 – 288Combined sources3
Helixi292 – 303Combined sources12
Beta strandi307 – 310Combined sources4
Turni311 – 314Combined sources4
Beta strandi316 – 318Combined sources3
Beta strandi321 – 323Combined sources3
Beta strandi331 – 333Combined sources3
Beta strandi335 – 337Combined sources3
Beta strandi339 – 341Combined sources3
Helixi342 – 350Combined sources9
Beta strandi361 – 364Combined sources4
Beta strandi370 – 375Combined sources6
Beta strandi380 – 382Combined sources3
Helixi384 – 386Combined sources3
Beta strandi387 – 389Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L5CNMR-A266-399[»]
2L5DNMR-A266-399[»]
3O3IX-ray2.80X277-399[»]
3O6EX-ray2.90X277-399[»]
3O7VX-ray2.10X276-399[»]
ProteinModelPortaliQ96J94.
SMRiQ96J94.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96J94.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini277 – 391PAZPROSITE-ProRule annotationAdd BLAST115
Domaini555 – 847PiwiPROSITE-ProRule annotationAdd BLAST293

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni316 – 318Required for binding 2'-O-methylated 3'-end of piRNAs3
Regioni540 – 677RNA-bindingBy similarityAdd BLAST138

Domaini

The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs.1 Publication

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.
HOGENOMiHOG000254789.
HOVERGENiHBG049411.
InParanoidiQ96J94.
KOiK02156.
OMAiPGYIQPR.
OrthoDBiEOG091G020J.
PhylomeDBiQ96J94.
TreeFamiTF354206.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR014811. ArgoL1.
IPR031320. GAGE.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR031326. PIWIL1.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERiPTHR22891:SF46. PTHR22891:SF46. 1 hit.
PfamiPF08699. ArgoL1. 1 hit.
PF05831. GAGE. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTiSM01379. GAGE. 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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96J94-1) [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 GRARGQETAQ LVGSTASQQP GYIQPRPQPP PAEGELFGRG
60 70 80 90 100
RQRGTAGGTA KSQGLQISAG FQELSLAERG GRRRDFHDLG VNTRQNLDHV
110 120 130 140 150
KESKTGSSGI IVRLSTNHFR LTSRPQWALY QYHIDYNPLM EARRLRSALL
160 170 180 190 200
FQHEDLIGKC HAFDGTILFL PKRLQQKVTE VFSKTRNGED VRITITLTNE
210 220 230 240 250
LPPTSPTCLQ FYNIIFRRLL KIMNLQQIGR NYYNPNDPID IPSHRLVIWP
260 270 280 290 300
GFTTSILQYE NSIMLCTDVS HKVLRSETVL DFMFNFYHQT EEHKFQEQVS
310 320 330 340 350
KELIGLVVLT KYNNKTYRVD DIDWDQNPKS TFKKADGSEV SFLEYYRKQY
360 370 380 390 400
NQEITDLKQP VLVSQPKRRR GPGGTLPGPA MLIPELCYLT GLTDKMRNDF
410 420 430 440 450
NVMKDLAVHT RLTPEQRQRE VGRLIDYIHK NDNVQRELRD WGLSFDSNLL
460 470 480 490 500
SFSGRILQTE KIHQGGKTFD YNPQFADWSK ETRGAPLISV KPLDNWLLIY
510 520 530 540 550
TRRNYEAANS LIQNLFKVTP AMGMQMRKAI MIEVDDRTEA YLRVLQQKVT
560 570 580 590 600
ADTQIVVCLL SSNRKDKYDA IKKYLCTDCP TPSQCVVART LGKQQTVMAI
610 620 630 640 650
ATKIALQMNC KMGGELWRVD IPLKLVMIVG IDCYHDMTAG RRSIAGFVAS
660 670 680 690 700
INEGMTRWFS RCIFQDRGQE LVDGLKVCLQ AALRAWNSCN EYMPSRIIVY
710 720 730 740 750
RDGVGDGQLK TLVNYEVPQF LDCLKSIGRG YNPRLTVIVV KKRVNTRFFA
760 770 780 790 800
QSGGRLQNPL PGTVIDVEVT RPEWYDFFIV SQAVRSGSVS PTHYNVIYDN
810 820 830 840 850
SGLKPDHIQR LTYKLCHIYY NWPGVIRVPA PCQYAHKLAF LVGQSIHREP
860
NLSLSNRLYY L
Length:861
Mass (Da):98,603
Last modified:December 1, 2001 - v1
Checksum:i58D7F6C7321DEFA4
GO
Isoform 2 (identifier: Q96J94-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     824-829: GVIRVP → VSASTC
     830-861: Missing.

Show »
Length:829
Mass (Da):94,845
Checksum:i03ADA415D1C159C3
GO
Isoform 3 (identifier: Q96J94-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-86: Missing.
     87-89: HDL → MIF

Show »
Length:775
Mass (Da):89,484
Checksum:iDF169A2E9EAFD916
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti178V → A in BAC04068 (PubMed:14702039).Curated1
Sequence conflicti314N → I in AAC97371 (PubMed:12037681).Curated1
Sequence conflicti339E → G in AAC97371 (PubMed:12037681).Curated1
Sequence conflicti353E → K in BAF49084 (PubMed:17544373).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026288491K → N.1 PublicationCorresponds to variant rs17856812dbSNPEnsembl.1
Natural variantiVAR_026289527R → K.1 PublicationCorresponds to variant rs1106042dbSNPEnsembl.1
Natural variantiVAR_026290575L → P.1 PublicationCorresponds to variant rs17852568dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0183661 – 86Missing in isoform 3. 1 PublicationAdd BLAST86
Alternative sequenceiVSP_01836787 – 89HDL → MIF in isoform 3. 1 Publication3
Alternative sequenceiVSP_018368824 – 829GVIRVP → VSASTC in isoform 2. 1 Publication6
Alternative sequenceiVSP_018369830 – 861Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF264004 mRNA. Translation: AAK92281.1.
AF104260 mRNA. Translation: AAC97371.2.
AF387507 mRNA. Translation: AAK69348.1.
AK093133 mRNA. Translation: BAC04068.1.
BC028581 mRNA. Translation: AAH28581.1.
AB274731 mRNA. Translation: BAF49084.1.
CCDSiCCDS9268.1. [Q96J94-1]
RefSeqiNP_001177900.1. NM_001190971.1. [Q96J94-2]
NP_004755.2. NM_004764.4. [Q96J94-1]
XP_011537304.1. XM_011539002.2. [Q96J94-1]
XP_011537305.1. XM_011539003.2. [Q96J94-1]
XP_011537306.1. XM_011539004.2. [Q96J94-1]
UniGeneiHs.405659.

Genome annotation databases

EnsembliENST00000245255; ENSP00000245255; ENSG00000125207. [Q96J94-1]
ENST00000613226; ENSP00000481042; ENSG00000275051. [Q96J94-1]
ENST00000632888; ENSP00000487688; ENSG00000275051. [Q96J94-2]
GeneIDi9271.
KEGGihsa:9271.
UCSCiuc001uik.4. human. [Q96J94-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF264004 mRNA. Translation: AAK92281.1.
AF104260 mRNA. Translation: AAC97371.2.
AF387507 mRNA. Translation: AAK69348.1.
AK093133 mRNA. Translation: BAC04068.1.
BC028581 mRNA. Translation: AAH28581.1.
AB274731 mRNA. Translation: BAF49084.1.
CCDSiCCDS9268.1. [Q96J94-1]
RefSeqiNP_001177900.1. NM_001190971.1. [Q96J94-2]
NP_004755.2. NM_004764.4. [Q96J94-1]
XP_011537304.1. XM_011539002.2. [Q96J94-1]
XP_011537305.1. XM_011539003.2. [Q96J94-1]
XP_011537306.1. XM_011539004.2. [Q96J94-1]
UniGeneiHs.405659.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L5CNMR-A266-399[»]
2L5DNMR-A266-399[»]
3O3IX-ray2.80X277-399[»]
3O6EX-ray2.90X277-399[»]
3O7VX-ray2.10X276-399[»]
ProteinModelPortaliQ96J94.
SMRiQ96J94.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114690. 7 interactors.
DIPiDIP-33534N.
IntActiQ96J94. 12 interactors.
STRINGi9606.ENSP00000245255.

PTM databases

iPTMnetiQ96J94.
PhosphoSitePlusiQ96J94.

Polymorphism and mutation databases

BioMutaiPIWIL1.
DMDMi74716803.

Proteomic databases

PaxDbiQ96J94.
PeptideAtlasiQ96J94.
PRIDEiQ96J94.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245255; ENSP00000245255; ENSG00000125207. [Q96J94-1]
ENST00000613226; ENSP00000481042; ENSG00000275051. [Q96J94-1]
ENST00000632888; ENSP00000487688; ENSG00000275051. [Q96J94-2]
GeneIDi9271.
KEGGihsa:9271.
UCSCiuc001uik.4. human. [Q96J94-1]

Organism-specific databases

CTDi9271.
DisGeNETi9271.
GeneCardsiPIWIL1.
HGNCiHGNC:9007. PIWIL1.
HPAiCAB012217.
HPA018798.
MIMi605571. gene.
neXtProtiNX_Q96J94.
OpenTargetsiENSG00000125207.
ENSG00000275051.
PharmGKBiPA33341.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1042. Eukaryota.
ENOG410XNRH. LUCA.
GeneTreeiENSGT00760000119148.
HOGENOMiHOG000254789.
HOVERGENiHBG049411.
InParanoidiQ96J94.
KOiK02156.
OMAiPGYIQPR.
OrthoDBiEOG091G020J.
PhylomeDBiQ96J94.
TreeFamiTF354206.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125207-MONOMER.
ReactomeiR-HSA-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Miscellaneous databases

EvolutionaryTraceiQ96J94.
GeneWikiiPIWIL1.
GenomeRNAii9271.
PROiQ96J94.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125207.
CleanExiHS_PIWIL1.
ExpressionAtlasiQ96J94. baseline and differential.
GenevisibleiQ96J94. HS.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR014811. ArgoL1.
IPR031320. GAGE.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR031326. PIWIL1.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERiPTHR22891:SF46. PTHR22891:SF46. 1 hit.
PfamiPF08699. ArgoL1. 1 hit.
PF05831. GAGE. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTiSM01379. GAGE. 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 nameiPIWL1_HUMAN
AccessioniPrimary (citable) accession number: Q96J94
Secondary accession number(s): A4F266
, O95404, Q8NA60, Q8TBY5, Q96JD5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 115 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 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.