ID   PIWL1_HUMAN             Reviewed;         861 AA.
AC   Q96J94; A4F266; O95404; Q8NA60; Q8TBY5; Q96JD5;
DT   16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 157.
DE   RecName: Full=Piwi-like protein 1;
DE            EC=3.1.26.- {ECO:0000250|UniProtKB:Q9JMB7};
GN   Name=PIWIL1;
GN   Synonyms=HIWI {ECO:0000303|PubMed:11154219,
GN   ECO:0000303|PubMed:28552346};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND INDUCTION.
RC   TISSUE=Testis;
RX   PubMed=11154219; DOI=10.1182/blood.v97.2.426;
RA   Sharma A.K., Nelson M.C., Brandt J.E., Wessman M., Mahmud N., Weller K.P.,
RA   Hoffman R.;
RT   "Human CD34+ stem cells express the hiwi gene, a human homologue of the
RT   Drosophila gene piwi.";
RL   Blood 97:426-434(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 3), AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Testis;
RX   PubMed=12037681; DOI=10.1038/sj.onc.1205505;
RA   Qiao D., Zeeman A.-M., Deng W., Looijenga L.H.J., Lin H.;
RT   "Molecular characterization of hiwi, a human member of the piwi gene family
RT   whose overexpression is correlated to seminomas.";
RL   Oncogene 21:3988-3999(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RA   Sha J.H.;
RT   "Cloning and identification of human piwi protein related to testis
RT   development.";
RL   Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Testis;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ASN-491;
RP   LYS-527 AND PRO-575.
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-530.
RX   PubMed=17544373; DOI=10.1016/j.bbrc.2007.05.136;
RA   Sugimoto K., Kage H., Aki N., Sano A., Kitagawa H., Nagase T., Yatomi Y.,
RA   Ohishi N., Takai D.;
RT   "The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus.";
RL   Biochem. Biophys. Res. Commun. 359:497-502(2007).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=12906857; DOI=10.1016/s0888-7543(03)00129-0;
RA   Sasaki T., Shiohama A., Minoshima S., Shimizu N.;
RT   "Identification of eight members of the Argonaute family in the human
RT   genome.";
RL   Genomics 82:323-330(2003).
RN   [8]
RP   INTERACTION WITH DICER1.
RX   PubMed=14749716; DOI=10.1038/sj.embor.7400070;
RA   Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C.;
RT   "Characterization of the interactions between mammalian PAZ PIWI domain
RT   proteins and Dicer.";
RL   EMBO Rep. 5:189-194(2004).
RN   [9]
RP   FUNCTION (ISOFORM 3).
RX   PubMed=16287078; DOI=10.1002/ijc.21575;
RA   Liu X., Sun Y., Guo J., Ma H., Li J., Dong B., Jin G., Zhang J., Wu J.,
RA   Meng L., Shou C.;
RT   "Expression of hiwi gene in human gastric cancer was associated with
RT   proliferation of cancer cells.";
RL   Int. J. Cancer 118:1922-1929(2006).
RN   [10]
RP   TISSUE SPECIFICITY.
RX   PubMed=23436708; DOI=10.1002/pmic.201200489;
RA   Liu M., Hu Z., Qi L., Wang J., Zhou T., Guo Y., Zeng Y., Zheng B., Wu Y.,
RA   Zhang P., Chen X., Tu W., Zhang T., Zhou Q., Jiang M., Guo X., Zhou Z.,
RA   Sha J.;
RT   "Scanning of novel cancer/testis proteins by human testis proteomic
RT   analysis.";
RL   Proteomics 13:1200-1210(2013).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 277-399 IN COMPLEX WITH METHYLATED
RP   SMALL RNA, DOMAIN PAZ, AND MUTAGENESIS OF PRO-379 AND MET-381.
RX   PubMed=21193640; DOI=10.1073/pnas.1017762108;
RA   Tian Y., Simanshu D.K., Ma J.B., Patel D.J.;
RT   "Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ
RT   (Piwi/Argonaute/Zwille) domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:903-910(2011).
RN   [12] {ECO:0007744|PDB:2L5C, ECO:0007744|PDB:2L5D}
RP   STRUCTURE BY NMR OF 266-399 IN COMPLEX WITH SMALL RNA, AND DOMAIN PAZ.
RX   PubMed=21465557; DOI=10.1002/prot.23003;
RA   Zeng L., Zhang Q., Yan K., Zhou M.M.;
RT   "Structural insights into piRNA recognition by the human PIWI-like 1 PAZ
RT   domain.";
RL   Proteins 79:2004-2009(2011).
RN   [13]
RP   VARIANTS ALA-217; ALA-220; ARG-220; GLY-220 AND HIS-224, INVOLVEMENT IN
RP   AZOOSPERMIA, AND UBIQUITINATION.
RX   PubMed=28552346; DOI=10.1016/j.cell.2017.04.034;
RA   Gou L.T., Kang J.Y., Dai P., Wang X., Li F., Zhao S., Zhang M., Hua M.M.,
RA   Lu Y., Zhu Y., Li Z., Chen H., Wu L.G., Li D., Fu X.D., Li J., Shi H.J.,
RA   Liu M.F.;
RT   "Ubiquitination-deficient mutations in human Piwi cause male infertility by
RT   impairing histone-to-protamine exchange during spermiogenesis.";
RL   Cell 169:1090-1104(2017).
CC   -!- FUNCTION: Endoribonuclease that plays a central role in postnatal germ
CC       cells by repressing transposable elements and preventing their
CC       mobilization, which is essential for the germline integrity. Acts via
CC       the piRNA metabolic process, which mediates the repression of
CC       transposable elements during meiosis by forming complexes composed of
CC       piRNAs and Piwi proteins and governs the methylation and subsequent
CC       repression of transposons. Directly binds methylated piRNAs, a class of
CC       24 to 30 nucleotide RNAs that are generated by a Dicer-independent
CC       mechanism and are primarily derived from transposons and other repeated
CC       sequence elements. Strongly prefers a uridine in the first position of
CC       their guide (g1U preference, also named 1U-bias). Not involved in the
CC       piRNA amplification loop, also named ping-pong amplification cycle.
CC       Acts as an endoribonuclease that cleaves transposon messenger RNAs.
CC       Besides their function in transposable elements repression, piRNAs are
CC       probably involved in other processes during meiosis such as translation
CC       regulation. Probable component of some RISC complex, which mediates RNA
CC       cleavage and translational silencing. Also plays a role in the
CC       formation of chromatoid bodies and is required for some miRNAs
CC       stability. Required to sequester RNF8 in the cytoplasm until late
CC       spermatogenesis; RNF8 being released upon ubiquitination and
CC       degradation of PIWIL1. {ECO:0000250|UniProtKB:Q9JMB7}.
CC   -!- FUNCTION: [Isoform 3]: May be a negative developmental regulator
CC       (PubMed:12037681, PubMed:16287078). {ECO:0000269|PubMed:12037681,
CC       ECO:0000269|PubMed:16287078}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q9JMB7};
CC   -!- SUBUNIT: Interacts (via Piwi domain) with DICER1, suggesting that it
CC       forms ribonucleoprotein RISC complexes; this interaction is regulated
CC       by HSP90AB1 activity. Interacts with MAEL, KIF17, PABPC1, PRMT5 and
CC       WDR77. Interacts (when methylated on arginine residues) with TDRD1,
CC       TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9. Interacts with CLOCK.
CC       Interacts with MOV10L1. Interacts with ANAPC10; interaction oly takes
CC       place following piRNA-binding. Interacts with RNF8; leading to
CC       sequester RNF8 in the cytoplasm. Interacts with TEX19 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JMB7}.
CC   -!- INTERACTION:
CC       Q96J94; P54253: ATXN1; NbExp=3; IntAct=EBI-527417, EBI-930964;
CC       Q96J94; Q9UPY3: DICER1; NbExp=2; IntAct=EBI-527417, EBI-395506;
CC       Q96J94; P50570-2: DNM2; NbExp=3; IntAct=EBI-527417, EBI-10968534;
CC       Q96J94; P42858: HTT; NbExp=3; IntAct=EBI-527417, EBI-466029;
CC       Q96J94; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-527417, EBI-1055254;
CC       Q96J94; Q7KZF4: SND1; NbExp=4; IntAct=EBI-527417, EBI-1044112;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9JMB7}.
CC       Note=Component of the meiotic nuage, also named P granule, a germ-cell-
CC       specific organelle required to repress transposon activity during
CC       meiosis. Also present in chromatoid body.
CC       {ECO:0000250|UniProtKB:Q9JMB7}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q96J94-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96J94-2; Sequence=VSP_018368, VSP_018369;
CC       Name=3;
CC         IsoId=Q96J94-3; Sequence=VSP_018366, VSP_018367;
CC   -!- TISSUE SPECIFICITY: Expressed in spermatocytes and spermatids. Also
CC       detected in prostate cancer (at protein level). Detected in most fetal
CC       and adult tissues. Expressed in testes, specifically in germline cells;
CC       detected in spermatocytes and spermatids during spermatogenesis.
CC       Increased expression in testicular tumors originating from embryonic
CC       germ cells with retention of germ cells phenotype. No expression in
CC       testicular tumors of somatic origin, such as Sertoli cell and Leydig
CC       cell tumors. Overexpressed in gastric cancer cells. Isoform 3:
CC       Ubiquitously expressed, and specifically in CD34(+) hematopoietic
CC       progenitor cells but not in more differentiated cells.
CC       {ECO:0000269|PubMed:11154219, ECO:0000269|PubMed:12037681,
CC       ECO:0000269|PubMed:12906857, ECO:0000269|PubMed:23436708}.
CC   -!- INDUCTION: [Isoform 3]: Down-regulated in CD34(+) hematopoietic cells
CC       during differentiation. {ECO:0000269|PubMed:11154219}.
CC   -!- DOMAIN: The PAZ domain specifically recognizes binds the 2'-O-
CC       methylated 3'-end of piRNAs (PubMed:21193640, PubMed:21465557). The MID
CC       region is required for recognition of uridine in the first position of
CC       piRNAs (g1U preference, also named 1U-bias) (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JMB7, ECO:0000269|PubMed:21193640,
CC       ECO:0000269|PubMed:21465557}.
CC   -!- DOMAIN: The D-box (destruction box) acts as a recognition signal for
CC       association with the APC/C complex, ubiquitination and degradation.
CC       {ECO:0000305|PubMed:28552346}.
CC   -!- PTM: Arginine methylation by PRMT5 is required for the interaction with
CC       Tudor domain-containing protein (TDRD1, TDRKH/TDRD2, RNF17/TDRD4,
CC       TDRD6, TDRD7 and TDRD9) and subsequent localization to the meiotic
CC       nuage, also named P granule. {ECO:0000250|UniProtKB:Q9JMB7}.
CC   -!- PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C)
CC       in late spermatids, leading to its degradation (PubMed:28552346).
CC       Ubiquitination only takes place following piRNA-binding in adult testis
CC       (By similarity). Ubiquitination and degradation in late spermatogenesis
CC       by APC/C is probably required to release RNF8 from the cytoplasm and
CC       promote histone to protamine exchange by RNF8 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JMB7, ECO:0000305|PubMed:28552346}.
CC   -!- DISEASE: Note=Defects in PIWIL1 may be a cause of a disorder resulting
CC       in the absence of sperm (azoospermia) in the semen, leading to male
CC       infertility. Male sterility can be caused by defects in ubiquitination
CC       and degradation during late spermatogenesis.
CC       {ECO:0000269|PubMed:28552346}.
CC   -!- SIMILARITY: Belongs to the argonaute family. Piwi subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AF264004; AAK92281.1; -; mRNA.
DR   EMBL; AF104260; AAC97371.2; -; mRNA.
DR   EMBL; AF387507; AAK69348.1; -; mRNA.
DR   EMBL; AK093133; BAC04068.1; -; mRNA.
DR   EMBL; BC028581; AAH28581.1; -; mRNA.
DR   EMBL; AB274731; BAF49084.1; -; mRNA.
DR   CCDS; CCDS9268.1; -. [Q96J94-1]
DR   RefSeq; NP_001177900.1; NM_001190971.1. [Q96J94-2]
DR   RefSeq; NP_004755.2; NM_004764.4. [Q96J94-1]
DR   RefSeq; XP_011537304.1; XM_011539002.2. [Q96J94-1]
DR   RefSeq; XP_011537305.1; XM_011539003.2. [Q96J94-1]
DR   RefSeq; XP_011537306.1; XM_011539004.2. [Q96J94-1]
DR   PDB; 2L5C; NMR; -; A=266-399.
DR   PDB; 2L5D; NMR; -; A=266-399.
DR   PDB; 3O3I; X-ray; 2.80 A; X=277-399.
DR   PDB; 3O6E; X-ray; 2.90 A; X=277-399.
DR   PDB; 3O7V; X-ray; 2.10 A; X=276-399.
DR   PDB; 6PI7; X-ray; 2.80 A; G=2-17.
DR   PDBsum; 2L5C; -.
DR   PDBsum; 2L5D; -.
DR   PDBsum; 3O3I; -.
DR   PDBsum; 3O6E; -.
DR   PDBsum; 3O7V; -.
DR   PDBsum; 6PI7; -.
DR   AlphaFoldDB; Q96J94; -.
DR   BMRB; Q96J94; -.
DR   SMR; Q96J94; -.
DR   BioGRID; 114690; 14.
DR   DIP; DIP-33534N; -.
DR   IntAct; Q96J94; 20.
DR   MINT; Q96J94; -.
DR   STRING; 9606.ENSP00000245255; -.
DR   iPTMnet; Q96J94; -.
DR   PhosphoSitePlus; Q96J94; -.
DR   BioMuta; PIWIL1; -.
DR   DMDM; 74716803; -.
DR   EPD; Q96J94; -.
DR   MassIVE; Q96J94; -.
DR   PaxDb; 9606-ENSP00000245255; -.
DR   PeptideAtlas; Q96J94; -.
DR   ProteomicsDB; 76913; -. [Q96J94-1]
DR   ProteomicsDB; 76914; -. [Q96J94-2]
DR   ProteomicsDB; 76915; -. [Q96J94-3]
DR   Antibodypedia; 31942; 347 antibodies from 38 providers.
DR   DNASU; 9271; -.
DR   Ensembl; ENST00000245255.7; ENSP00000245255.3; ENSG00000125207.7. [Q96J94-1]
DR   Ensembl; ENST00000613226.2; ENSP00000481042.1; ENSG00000275051.2. [Q96J94-1]
DR   Ensembl; ENST00000632888.1; ENSP00000487688.1; ENSG00000275051.2. [Q96J94-2]
DR   GeneID; 9271; -.
DR   KEGG; hsa:9271; -.
DR   MANE-Select; ENST00000245255.7; ENSP00000245255.3; NM_004764.5; NP_004755.2.
DR   UCSC; uc001uik.4; human. [Q96J94-1]
DR   AGR; HGNC:9007; -.
DR   CTD; 9271; -.
DR   DisGeNET; 9271; -.
DR   GeneCards; PIWIL1; -.
DR   HGNC; HGNC:9007; PIWIL1.
DR   HPA; ENSG00000125207; Tissue enriched (testis).
DR   MIM; 605571; gene.
DR   neXtProt; NX_Q96J94; -.
DR   OpenTargets; ENSG00000125207; -.
DR   PharmGKB; PA33341; -.
DR   VEuPathDB; HostDB:ENSG00000125207; -.
DR   eggNOG; KOG1042; Eukaryota.
DR   GeneTree; ENSGT00950000183200; -.
DR   HOGENOM; CLU_008813_0_0_1; -.
DR   InParanoid; Q96J94; -.
DR   OMA; NPTMSRW; -.
DR   OrthoDB; 3060088at2759; -.
DR   PhylomeDB; Q96J94; -.
DR   TreeFam; TF354206; -.
DR   PathwayCommons; Q96J94; -.
DR   Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis.
DR   SignaLink; Q96J94; -.
DR   SIGNOR; Q96J94; -.
DR   BioGRID-ORCS; 9271; 12 hits in 1151 CRISPR screens.
DR   ChiTaRS; PIWIL1; human.
DR   EvolutionaryTrace; Q96J94; -.
DR   GeneWiki; PIWIL1; -.
DR   GenomeRNAi; 9271; -.
DR   Pharos; Q96J94; Tbio.
DR   PRO; PR:Q96J94; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q96J94; Protein.
DR   Bgee; ENSG00000125207; Expressed in right testis and 63 other cell types or tissues.
DR   ExpressionAtlas; Q96J94; baseline and differential.
DR   GO; GO:0033391; C:chromatoid body; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0097433; C:dense body; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR   GO; GO:0043186; C:P granule; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR   GO; GO:0140262; F:mRNA cap binding complex binding; IEA:Ensembl.
DR   GO; GO:0034584; F:piRNA binding; IDA:UniProtKB.
DR   GO; GO:1905538; F:polysome binding; IEA:Ensembl.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0004521; F:RNA endonuclease activity; ISS:UniProtKB.
DR   GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl.
DR   GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0141006; P:piRNA-mediated retrotransposon silencing by heterochromatin formation; ISS:UniProtKB.
DR   GO; GO:0140990; P:primary piRNA processing; ISS:UniProtKB.
DR   GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR   GO; GO:0031047; P:regulatory ncRNA-mediated gene silencing; ISS:UniProtKB.
DR   GO; GO:0035092; P:sperm DNA condensation; ISS:UniProtKB.
DR   GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR   CDD; cd02845; PAZ_piwi_like; 1.
DR   CDD; cd04658; Piwi_piwi-like_Euk; 1.
DR   Gene3D; 3.40.50.2300; -; 1.
DR   Gene3D; 2.170.260.10; paz domain; 1.
DR   Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1.
DR   InterPro; IPR014811; ArgoL1.
DR   InterPro; IPR031320; GAGE.
DR   InterPro; IPR003100; PAZ_dom.
DR   InterPro; IPR036085; PAZ_dom_sf.
DR   InterPro; IPR003165; Piwi.
DR   InterPro; IPR012337; RNaseH-like_sf.
DR   InterPro; IPR036397; RNaseH_sf.
DR   PANTHER; PTHR22891; EUKARYOTIC TRANSLATION INITIATION FACTOR 2C; 1.
DR   PANTHER; PTHR22891:SF46; PIWI-LIKE PROTEIN 1; 1.
DR   Pfam; PF08699; ArgoL1; 1.
DR   Pfam; PF05831; GAGE; 1.
DR   Pfam; PF02170; PAZ; 1.
DR   Pfam; PF02171; Piwi; 1.
DR   SMART; SM01379; GAGE; 1.
DR   SMART; SM00949; PAZ; 1.
DR   SMART; SM00950; Piwi; 1.
DR   SUPFAM; SSF101690; PAZ domain; 1.
DR   SUPFAM; SSF53098; Ribonuclease H-like; 1.
DR   PROSITE; PS50821; PAZ; 1.
DR   PROSITE; PS50822; PIWI; 1.
DR   Genevisible; Q96J94; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW   Differentiation; Disease variant; Endonuclease; Hydrolase; Magnesium;
KW   Meiosis; Metal-binding; Methylation; Nuclease; Reference proteome;
KW   RNA-binding; RNA-mediated gene silencing; Spermatogenesis;
KW   Translation regulation; Ubl conjugation.
FT   CHAIN           1..861
FT                   /note="Piwi-like protein 1"
FT                   /id="PRO_0000234567"
FT   DOMAIN          278..391
FT                   /note="PAZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT   DOMAIN          555..847
FT                   /note="Piwi"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00150"
FT   REGION          1..64
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          316..318
FT                   /note="Required for binding 2'-O-methylated 3'-end of
FT                   piRNAs"
FT                   /evidence="ECO:0000269|PubMed:21193640"
FT   REGION          479..615
FT                   /note="MID region"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   MOTIF           217..224
FT                   /note="D-box"
FT                   /evidence="ECO:0000269|PubMed:28552346"
FT   COMPBIAS        18..32
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        632
FT                   /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT   ACT_SITE        670
FT                   /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT   ACT_SITE        702
FT                   /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT   ACT_SITE        836
FT                   /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT   SITE            381
FT                   /note="Required for binding 2'-O-methylated 3'-end of
FT                   piRNAs"
FT                   /evidence="ECO:0000269|PubMed:21193640"
FT   MOD_RES         14
FT                   /note="Omega-N-methylarginine; by PRMT5; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   MOD_RES         14
FT                   /note="Symmetric dimethylarginine; by PRMT5; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   MOD_RES         49
FT                   /note="Omega-N-methylarginine; by PRMT5"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   MOD_RES         53
FT                   /note="Omega-N-methylarginine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   MOD_RES         53
FT                   /note="Symmetric dimethylarginine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   MOD_RES         370
FT                   /note="Omega-N-methylarginine; by PRMT5"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMB7"
FT   VAR_SEQ         1..86
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11154219"
FT                   /id="VSP_018366"
FT   VAR_SEQ         87..89
FT                   /note="HDL -> MIF (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11154219"
FT                   /id="VSP_018367"
FT   VAR_SEQ         824..829
FT                   /note="GVIRVP -> VSASTC (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_018368"
FT   VAR_SEQ         830..861
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_018369"
FT   VARIANT         217
FT                   /note="R -> A (found in a patient with azoospermia; likely
FT                   pathogenic; requires 2 nucleotide substitutions)"
FT                   /evidence="ECO:0000269|PubMed:28552346"
FT                   /id="VAR_078965"
FT   VARIANT         220
FT                   /note="L -> A (found in a patient with azoospermia; likely
FT                   pathogenic; requires 2 nucleotide substitutions)"
FT                   /evidence="ECO:0000269|PubMed:28552346"
FT                   /id="VAR_078966"
FT   VARIANT         220
FT                   /note="L -> G (found in a patient with azoospermia; likely
FT                   pathogenic; requires 2 nucleotide substitutions)"
FT                   /evidence="ECO:0000269|PubMed:28552346"
FT                   /id="VAR_078967"
FT   VARIANT         220
FT                   /note="L -> R (found in a patient with azoospermia; likely
FT                   pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:28552346"
FT                   /id="VAR_078968"
FT   VARIANT         224
FT                   /note="N -> H (found in a patient with azoospermia; likely
FT                   pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:28552346"
FT                   /id="VAR_078969"
FT   VARIANT         491
FT                   /note="K -> N (in dbSNP:rs17856812)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_026288"
FT   VARIANT         527
FT                   /note="R -> K (in dbSNP:rs1106042)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_026289"
FT   VARIANT         575
FT                   /note="L -> P (in dbSNP:rs17852568)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_026290"
FT   MUTAGEN         379
FT                   /note="P->H: Impairs binding to 2'-O-methylated 3'-end of
FT                   piRNAs; when associated with Y-381."
FT                   /evidence="ECO:0000269|PubMed:21193640"
FT   MUTAGEN         381
FT                   /note="M->Y: Impairs binding to 2'-O-methylated 3'-end of
FT                   piRNAs; when associated with H-379."
FT                   /evidence="ECO:0000269|PubMed:21193640"
FT   CONFLICT        178
FT                   /note="V -> A (in Ref. 4; BAC04068)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        314
FT                   /note="N -> I (in Ref. 2; AAC97371)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        339
FT                   /note="E -> G (in Ref. 2; AAC97371)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        353
FT                   /note="E -> K (in Ref. 6; BAF49084)"
FT                   /evidence="ECO:0000305"
FT   HELIX           279..285
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   HELIX           286..288
FT                   /evidence="ECO:0007829|PDB:2L5D"
FT   HELIX           292..303
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          307..310
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   TURN            311..314
FT                   /evidence="ECO:0007829|PDB:2L5C"
FT   STRAND          316..318
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          321..323
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          331..333
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          335..337
FT                   /evidence="ECO:0007829|PDB:2L5C"
FT   STRAND          339..341
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   HELIX           342..350
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          361..364
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          370..375
FT                   /evidence="ECO:0007829|PDB:2L5C"
FT   STRAND          380..382
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   HELIX           384..386
FT                   /evidence="ECO:0007829|PDB:3O7V"
FT   STRAND          387..389
FT                   /evidence="ECO:0007829|PDB:3O6E"
SQ   SEQUENCE   861 AA;  98603 MW;  58D7F6C7321DEFA4 CRC64;
     MTGRARARAR GRARGQETAQ LVGSTASQQP GYIQPRPQPP PAEGELFGRG RQRGTAGGTA
     KSQGLQISAG FQELSLAERG GRRRDFHDLG VNTRQNLDHV KESKTGSSGI IVRLSTNHFR
     LTSRPQWALY QYHIDYNPLM EARRLRSALL FQHEDLIGKC HAFDGTILFL PKRLQQKVTE
     VFSKTRNGED VRITITLTNE LPPTSPTCLQ FYNIIFRRLL KIMNLQQIGR NYYNPNDPID
     IPSHRLVIWP GFTTSILQYE NSIMLCTDVS HKVLRSETVL DFMFNFYHQT EEHKFQEQVS
     KELIGLVVLT KYNNKTYRVD DIDWDQNPKS TFKKADGSEV SFLEYYRKQY NQEITDLKQP
     VLVSQPKRRR GPGGTLPGPA MLIPELCYLT GLTDKMRNDF NVMKDLAVHT RLTPEQRQRE
     VGRLIDYIHK NDNVQRELRD WGLSFDSNLL SFSGRILQTE KIHQGGKTFD YNPQFADWSK
     ETRGAPLISV KPLDNWLLIY TRRNYEAANS LIQNLFKVTP AMGMQMRKAI MIEVDDRTEA
     YLRVLQQKVT ADTQIVVCLL SSNRKDKYDA IKKYLCTDCP TPSQCVVART LGKQQTVMAI
     ATKIALQMNC KMGGELWRVD IPLKLVMIVG IDCYHDMTAG RRSIAGFVAS INEGMTRWFS
     RCIFQDRGQE LVDGLKVCLQ AALRAWNSCN EYMPSRIIVY RDGVGDGQLK TLVNYEVPQF
     LDCLKSIGRG YNPRLTVIVV KKRVNTRFFA QSGGRLQNPL PGTVIDVEVT RPEWYDFFIV
     SQAVRSGSVS PTHYNVIYDN SGLKPDHIQR LTYKLCHIYY NWPGVIRVPA PCQYAHKLAF
     LVGQSIHREP NLSLSNRLYY L
//