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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

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. 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. Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle. Acts as an endoribonuclease that cleaves transposon messenger RNAs. 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. Required to sequester RNF8 in the cytoplasm until late spermatogenesis; RNF8 being released upon ubiquitination and degradation of PIWIL1.By similarity
Isoform 3: May be a negative developmental regulator (PubMed:12037681, PubMed:16287078).2 Publications

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei381Required for binding 2'-O-methylated 3'-end of piRNAs1 Publication1
Active sitei632By similarity1
Active sitei670By similarity1
Active sitei702By similarity1
Active sitei836By similarity1

GO - Molecular functioni

GO - Biological processi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 1 (EC:3.1.26.-By similarity)
Gene namesi
Name:PIWIL1
Synonyms:HIWI2 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000125207.7.
HGNCiHGNC:9007. 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

Involvement in diseasei

Defects in PIWIL1 may be a cause of a disorder resulting in the absence of sperm (azoospermia) in the semen, leading to male infertility. Male sterility can be caused by defects in ubiquitination and degradation during late spermatogenesis.1 Publication

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

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi9271.
OpenTargetsiENSG00000125207.
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
Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in late spermatids, leading to its degradation (PubMed:28552346). Ubiquitination only takes place following piRNA-binding in adult testis (By similarity). 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 (By similarity).By similarity1 Publication

Keywords - PTMi

Methylation, Ubl conjugation

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: Ubiquitously expressed, and specifically in CD34+ hematopoietic progenitor cells but not in more differentiated cells.4 Publications

Inductioni

Isoform 3: 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. Interacts with ANAPC10; interaction oly takes place following piRNA-binding. Interacts with RNF8; leading to sequester RNF8 in the cytoplasm. Interacts with TEX19 (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114690. 7 interactors.
DIPiDIP-33534N.
IntActiQ96J94. 14 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 piRNAs1 Publication3
Regioni479 – 615MID regionBy similarityAdd BLAST137

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi217 – 224D-box1 Publication8

Domaini

The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs (PubMed:21193640, PubMed:21465557). The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias) (By similarity).By similarity2 Publications
The D-box (destruction box) acts as a recognition signal for association with the APC/C complex, ubiquitination and degradation.1 Publication

Sequence similaritiesi

Belongs to the argonaute family. Piwi subfamily.Curated

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.
InterProiView protein in InterPro
IPR014811. ArgoL1.
IPR031320. GAGE.
IPR003100. PAZ_dom.
IPR036085. PAZ_dom_sf.
IPR003165. Piwi.
IPR031326. PIWIL1.
IPR012337. RNaseH-like_sf.
IPR036397. RNaseH_sf.
PANTHERiPTHR22891:SF46. PTHR22891:SF46. 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 (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_078965217R → A Probable disease-associated mutation found in a patient with azoospermia; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_078966220L → A Probable disease-associated mutation found in a patient with azoospermia; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_078967220L → G Probable disease-associated mutation found in a patient with azoospermia; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_078968220L → R Probable disease-associated mutation found in a patient with azoospermia. 1 Publication1
Natural variantiVAR_078969224N → H Probable disease-associated mutation found in a patient with azoospermia. 1 Publication1
Natural variantiVAR_026288491K → N1 PublicationCorresponds to variant dbSNP:rs17856812Ensembl.1
Natural variantiVAR_026289527R → K1 PublicationCorresponds to variant dbSNP:rs1106042Ensembl.1
Natural variantiVAR_026290575L → P1 PublicationCorresponds to variant dbSNP:rs17852568Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiPIWL1_HUMAN
AccessioniPrimary (citable) accession number: Q96J94
Secondary accession number(s): A4F266
, O95404, Q8NA60, Q8TBY5, Q96JD5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: December 1, 2001
Last modified: October 25, 2017
This is version 122 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. 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