{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q96J94","secondaryAccessions":["A4F266","O95404","Q8NA60","Q8TBY5","Q96JD5"],"uniProtkbId":"PIWL1_HUMAN","entryAudit":{"firstPublicDate":"2006-05-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-12-01","entryVersion":167,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Piwi-like protein 1"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"}],"value":"3.1.26.-"}]}},"genes":[{"geneName":{"value":"PIWIL1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11154219"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"28552346"}],"value":"HIWI"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"}],"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12037681"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16287078"}],"value":"May be a negative developmental regulator (PubMed:12037681, PubMed:16287078)"}],"commentType":"FUNCTION","molecule":"Isoform 3"},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14749716"}],"value":"Interacts (via Piwi domain) with DICER1, suggesting that it forms ribonucleoprotein RISC complexes; this interaction is regulated by HSP90AB1 activity (PubMed:14749716). 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). Interacts with FAM170A (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q96J94","intActId":"EBI-527417"},"interactantTwo":{"uniProtKBAccession":"P54253","geneName":"ATXN1","intActId":"EBI-930964"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96J94","intActId":"EBI-527417"},"interactantTwo":{"uniProtKBAccession":"Q9UPY3","geneName":"DICER1","intActId":"EBI-395506"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96J94","intActId":"EBI-527417"},"interactantTwo":{"uniProtKBAccession":"P50570-2","geneName":"DNM2","intActId":"EBI-10968534"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96J94","intActId":"EBI-527417"},"interactantTwo":{"uniProtKBAccession":"P42858","geneName":"HTT","intActId":"EBI-466029"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96J94","intActId":"EBI-527417"},"interactantTwo":{"uniProtKBAccession":"Q8WXH2","geneName":"JPH3","intActId":"EBI-1055254"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96J94","intActId":"EBI-527417"},"interactantTwo":{"uniProtKBAccession":"Q7KZF4","geneName":"SND1","intActId":"EBI-1044112"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"}],"value":"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"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q96J94-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q96J94-2"],"sequenceIds":["VSP_018368","VSP_018369"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q96J94-3"],"sequenceIds":["VSP_018366","VSP_018367"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11154219"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12037681"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12906857"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23436708"}],"value":"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"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11154219"}],"value":"Down-regulated in CD34(+) hematopoietic cells during differentiation"}],"commentType":"INDUCTION","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21193640"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21465557"}],"value":"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)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28552346"}],"value":"The D-box (destruction box) acts as a recognition signal for association with the APC/C complex, ubiquitination and degradation"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"}],"value":"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"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JMB7"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28552346"}],"value":"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)"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28552346"}],"value":"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"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the argonaute family. 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