PIWL1_HUMAN
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 03-AUG-2022, entry version 149.
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, 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; Q96J94; -.
DR PeptideAtlas; Q96J94; -.
DR PRIDE; Q96J94; -.
DR ProteomicsDB; 76913; -. [Q96J94-1]
DR ProteomicsDB; 76914; -. [Q96J94-2]
DR ProteomicsDB; 76915; -. [Q96J94-3]
DR Antibodypedia; 31942; 288 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 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; 220258at2759; -.
DR PhylomeDB; Q96J94; -.
DR TreeFam; TF354206; -.
DR PathwayCommons; Q96J94; -.
DR Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis.
DR SignaLink; Q96J94; -.
DR BioGRID-ORCS; 9271; 12 hits in 1071 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 61 other tissues.
DR ExpressionAtlas; Q96J94; baseline and differential.
DR Genevisible; Q96J94; HS.
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:0004521; F:endoribonuclease activity; 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:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0010529; P:negative regulation of transposition; ISS:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; ISS:UniProtKB.
DR Gene3D; 3.30.420.10; -; 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; IPR031326; PIWIL1.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR PANTHER; PTHR22891:SF46; PTHR22891:SF46; 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; SSF101690; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS50822; PIWI; 1.
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 277..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 (probable disease-associated variant found in
FT a patient with azoospermia; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:28552346"
FT /id="VAR_078965"
FT VARIANT 220
FT /note="L -> A (probable disease-associated variant found in
FT a patient with azoospermia; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:28552346"
FT /id="VAR_078966"
FT VARIANT 220
FT /note="L -> G (probable disease-associated variant found in
FT a patient with azoospermia; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:28552346"
FT /id="VAR_078967"
FT VARIANT 220
FT /note="L -> R (probable disease-associated variant found in
FT a patient with azoospermia)"
FT /evidence="ECO:0000269|PubMed:28552346"
FT /id="VAR_078968"
FT VARIANT 224
FT /note="N -> H (probable disease-associated variant found in
FT a patient with azoospermia)"
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
