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Q96J94 (PIWL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Piwi-like protein 1
Gene names
Name:PIWIL1
Synonyms:HIWI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length861 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.8 Ref.9

Subunit structure

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 By similarity. Ref.8

Subcellular location

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.

Tissue specificity

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. Ref.1 Ref.2 Ref.7 Ref.10

Induction

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

Domain

The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs. Ref.11

Post-translational modification

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.

Sequence similarities

Belongs to the argonaute family. Piwi subfamily.

Contains 1 PAZ domain.

Contains 1 Piwi domain.

Ontologies

Keywords
   Biological processDifferentiation
Meiosis
RNA-mediated gene silencing
Spermatogenesis
Translation regulation
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandRNA-binding
   Molecular functionDevelopmental protein
   PTMMethylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processgene silencing by RNA

Inferred from sequence or structural similarity. Source: UniProtKB

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

piRNA metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

spermatid development

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentP granule

Inferred from sequence or structural similarity. Source: UniProtKB

chromatoid body

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

mRNA cap binding complex

Inferred from electronic annotation. Source: Ensembl

polysome

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionmRNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

piRNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: IntAct

single-stranded RNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DICER1Q9UPY32EBI-527417,EBI-395506

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96J94-1)

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.
Isoform 2 (identifier: Q96J94-2)

The sequence of this isoform differs from the canonical sequence as follows:
     824-829: GVIRVP → VSASTC
     830-861: Missing.
Isoform 3 (identifier: Q96J94-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 861861Piwi-like protein 1
PRO_0000234567

Regions

Domain277 – 391115PAZ
Domain555 – 847293Piwi
Region316 – 3183Required for binding 2'-O-methylated 3'-end of piRNAs
Region540 – 677138RNA-binding By similarity

Sites

Site3811Required for binding 2'-O-methylated 3'-end of piRNAs

Amino acid modifications

Modified residue141Omega-N-methylarginine; by PRMT5; alternate By similarity
Modified residue141Symmetric dimethylarginine; by PRMT5; alternate By similarity
Modified residue491Omega-N-methylarginine; by PRMT5 By similarity
Modified residue531Omega-N-methylarginine By similarity
Modified residue3701Omega-N-methylarginine; by PRMT5 By similarity

Natural variations

Alternative sequence1 – 8686Missing in isoform 3.
VSP_018366
Alternative sequence87 – 893HDL → MIF in isoform 3.
VSP_018367
Alternative sequence824 – 8296GVIRVP → VSASTC in isoform 2.
VSP_018368
Alternative sequence830 – 86132Missing in isoform 2.
VSP_018369
Natural variant4911K → N. Ref.5
Corresponds to variant rs17856812 [ dbSNP | Ensembl ].
VAR_026288
Natural variant5271R → K. Ref.5
Corresponds to variant rs1106042 [ dbSNP | Ensembl ].
VAR_026289
Natural variant5751L → P. Ref.5
Corresponds to variant rs17852568 [ dbSNP | Ensembl ].
VAR_026290

Experimental info

Mutagenesis3791P → H: Impairs binding to 2'-O-methylated 3'-end of piRNAs; when associated with Y-381. Ref.11
Mutagenesis3811M → Y: Impairs binding to 2'-O-methylated 3'-end of piRNAs; when associated with H-379. Ref.11
Sequence conflict1781V → A in BAC04068. Ref.4
Sequence conflict3141N → I in AAC97371. Ref.2
Sequence conflict3391E → G in AAC97371. Ref.2
Sequence conflict3531E → K in BAF49084. Ref.6

Secondary structure

............................. 861
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 58D7F6C7321DEFA4

FASTA86198,603
        10         20         30         40         50         60 
MTGRARARAR GRARGQETAQ LVGSTASQQP GYIQPRPQPP PAEGELFGRG RQRGTAGGTA 

        70         80         90        100        110        120 
KSQGLQISAG FQELSLAERG GRRRDFHDLG VNTRQNLDHV KESKTGSSGI IVRLSTNHFR 

       130        140        150        160        170        180 
LTSRPQWALY QYHIDYNPLM EARRLRSALL FQHEDLIGKC HAFDGTILFL PKRLQQKVTE 

       190        200        210        220        230        240 
VFSKTRNGED VRITITLTNE LPPTSPTCLQ FYNIIFRRLL KIMNLQQIGR NYYNPNDPID 

       250        260        270        280        290        300 
IPSHRLVIWP GFTTSILQYE NSIMLCTDVS HKVLRSETVL DFMFNFYHQT EEHKFQEQVS 

       310        320        330        340        350        360 
KELIGLVVLT KYNNKTYRVD DIDWDQNPKS TFKKADGSEV SFLEYYRKQY NQEITDLKQP 

       370        380        390        400        410        420 
VLVSQPKRRR GPGGTLPGPA MLIPELCYLT GLTDKMRNDF NVMKDLAVHT RLTPEQRQRE 

       430        440        450        460        470        480 
VGRLIDYIHK NDNVQRELRD WGLSFDSNLL SFSGRILQTE KIHQGGKTFD YNPQFADWSK 

       490        500        510        520        530        540 
ETRGAPLISV KPLDNWLLIY TRRNYEAANS LIQNLFKVTP AMGMQMRKAI MIEVDDRTEA 

       550        560        570        580        590        600 
YLRVLQQKVT ADTQIVVCLL SSNRKDKYDA IKKYLCTDCP TPSQCVVART LGKQQTVMAI 

       610        620        630        640        650        660 
ATKIALQMNC KMGGELWRVD IPLKLVMIVG IDCYHDMTAG RRSIAGFVAS INEGMTRWFS 

       670        680        690        700        710        720 
RCIFQDRGQE LVDGLKVCLQ AALRAWNSCN EYMPSRIIVY RDGVGDGQLK TLVNYEVPQF 

       730        740        750        760        770        780 
LDCLKSIGRG YNPRLTVIVV KKRVNTRFFA QSGGRLQNPL PGTVIDVEVT RPEWYDFFIV 

       790        800        810        820        830        840 
SQAVRSGSVS PTHYNVIYDN SGLKPDHIQR LTYKLCHIYY NWPGVIRVPA PCQYAHKLAF 

       850        860 
LVGQSIHREP NLSLSNRLYY L 

« Hide

Isoform 2 [UniParc].

Checksum: 03ADA415D1C159C3
Show »

FASTA82994,845
Isoform 3 [UniParc].

Checksum: DF169A2E9EAFD916
Show »

FASTA77589,484

References

« Hide 'large scale' references
[1]"Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi."
Sharma A.K., Nelson M.C., Brandt J.E., Wessman M., Mahmud N., Weller K.P., Hoffman R.
Blood 97:426-434(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, INDUCTION.
Tissue: Testis.
[2]"Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas."
Qiao D., Zeeman A.-M., Deng W., Looijenga L.H.J., Lin H.
Oncogene 21:3988-3999(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Tissue: Testis.
[3]"Cloning and identification of human piwi protein related to testis development."
Sha J.H.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Testis.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ASN-491; LYS-527 AND PRO-575.
Tissue: Testis.
[6]"The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus."
Sugimoto K., Kage H., Aki N., Sano A., Kitagawa H., Nagase T., Yatomi Y., Ohishi N., Takai D.
Biochem. Biophys. Res. Commun. 359:497-502(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-530.
[7]"Identification of eight members of the Argonaute family in the human genome."
Sasaki T., Shiohama A., Minoshima S., Shimizu N.
Genomics 82:323-330(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer."
Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C.
EMBO Rep. 5:189-194(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DICER1, FUNCTION.
[9]"Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells."
Liu X., Sun Y., Guo J., Ma H., Li J., Dong B., Jin G., Zhang J., Wu J., Meng L., Shou C.
Int. J. Cancer 118:1922-1929(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Scanning of novel cancer/testis proteins by human testis proteomic analysis."
Liu M., Hu Z., Qi L., Wang J., Zhou T., Guo Y., Zeng Y., Zheng B., Wu Y., Zhang P., Chen X., Tu W., Zhang T., Zhou Q., Jiang M., Guo X., Zhou Z., Sha J.
Proteomics 13:1200-1210(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[11]"Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains."
Tian Y., Simanshu D.K., Ma J.B., Patel D.J.
Proc. Natl. Acad. Sci. U.S.A. 108:903-910(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 277-399 IN COMPLEX WITH METHYLATED SMALL RNA, DOMAIN PAZ, MUTAGENESIS OF PRO-379 AND MET-381.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS9268.1. [Q96J94-1]
RefSeqNP_001177900.1. NM_001190971.1. [Q96J94-2]
NP_004755.2. NM_004764.4. [Q96J94-1]
XP_005253689.1. XM_005253632.2. [Q96J94-1]
XP_006719761.1. XM_006719698.1. [Q96J94-1]
UniGeneHs.405659.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L5CNMR-A266-399[»]
2L5DNMR-A266-399[»]
3O3IX-ray2.80X277-399[»]
3O6EX-ray2.90X277-399[»]
3O7VX-ray2.10X276-399[»]
ProteinModelPortalQ96J94.
SMRQ96J94. Positions 106-840.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114690. 5 interactions.
DIPDIP-33534N.
IntActQ96J94. 1 interaction.
STRING9606.ENSP00000245255.

PTM databases

PhosphoSiteQ96J94.

Polymorphism databases

DMDM74716803.

Proteomic databases

PaxDbQ96J94.
PRIDEQ96J94.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245255; ENSP00000245255; ENSG00000125207. [Q96J94-1]
GeneID9271.
KEGGhsa:9271.
UCSCuc001uij.2. human. [Q96J94-2]
uc001uik.3. human. [Q96J94-1]

Organism-specific databases

CTD9271.
GeneCardsGC12P130822.
HGNCHGNC:9007. PIWIL1.
HPACAB012217.
HPA018798.
MIM605571. gene.
neXtProtNX_Q96J94.
PharmGKBPA33341.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG286051.
HOGENOMHOG000254789.
HOVERGENHBG049411.
InParanoidQ96J94.
KOK02156.
OMAPGYIQPR.
OrthoDBEOG712TVQ.
PhylomeDBQ96J94.
TreeFamTF354206.

Gene expression databases

ArrayExpressQ96J94.
BgeeQ96J94.
CleanExHS_PIWIL1.
GenevestigatorQ96J94.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
InterProIPR008625. GAGE.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamPF05831. GAGE. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTSM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96J94.
GeneWikiPIWIL1.
GenomeRNAi9271.
NextBio34751.
PROQ96J94.
SOURCESearch...

Entry information

Entry namePIWL1_HUMAN
AccessionPrimary (citable) accession number: Q96J94
Secondary accession number(s): A4F266 expand/collapse secondary AC list , O95404, Q8NA60, Q8TBY5, Q96JD5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM