PIWL4_RAT
ID PIWL4_RAT Reviewed; 848 AA.
AC Q4G033;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 25-MAY-2022, entry version 71.
DE RecName: Full=Piwi-like protein 4;
GN Name=Piwil4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 393-848.
RC TISSUE=Spleen;
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=24930433; DOI=10.1002/hep.27267;
RA Rizzo F., Hashim A., Marchese G., Ravo M., Tarallo R., Nassa G.,
RA Giurato G., Rinaldi A., Cordella A., Persico M., Sulas P., Perra A.,
RA Ledda-Columbano G.M., Columbano A., Weisz A.;
RT "Timed regulation of P-element-induced wimpy testis-interacting RNA
RT expression during rat liver regeneration.";
RL Hepatology 60:798-806(2014).
RN [4]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=28711973; DOI=10.1007/s00125-017-4368-2;
RA Henaoui I.S., Jacovetti C., Guerra Mollet I., Guay C., Sobel J.,
RA Eliasson L., Regazzi R.;
RT "PIWI-interacting RNAs as novel regulators of pancreatic beta cell
RT function.";
RL Diabetologia 60:1977-1986(2017).
CC -!- FUNCTION: Plays a central role during spermatogenesis by repressing
CC transposable elements and preventing their mobilization, which is
CC essential for the germline integrity. Acts via the piRNA metabolic
CC process, which mediates the repression of transposable elements during
CC meiosis by forming complexes composed of piRNAs and Piwi proteins and
CC governs the methylation and subsequent repression of transposons.
CC Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are
CC generated by a Dicer-independent mechanism and are primarily derived
CC from transposons and other repeated sequence elements. Associates with
CC secondary piRNAs antisense and PIWIL2/MILI is required for such
CC association. The piRNA process acts upstream of known mediators of DNA
CC methylation. Does not show endonuclease activity. Plays a key role in
CC the piRNA amplification loop, also named ping-pong amplification cycle,
CC by acting as a 'slicer-incompetent' component that loads cleaved piRNAs
CC from the 'slicer-competent' component PIWIL2 and target them on genomic
CC transposon loci in the nucleus. In addition to its role in germline,
CC PIWIL4 also plays a role in the regulation of somatic cells activities.
CC Plays a role in pancreatic beta cell function and insulin secretion
CC (PubMed:28711973). Involved in maintaining cell morphology and
CC functional integrity of retinal epithelial through Akt/GSK3alpha/beta
CC signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q7Z3Z4,
CC ECO:0000250|UniProtKB:Q8CGT6, ECO:0000269|PubMed:28711973}.
CC -!- SUBUNIT: Interacts with PRMT5 and WDR77. Interacts (when methylated on
CC arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9. Interacts with
CC MOV10L1 (By similarity). Interacts with TEX15 and SPOCD1 (By
CC similarity). {ECO:0000250|UniProtKB:Q8CGT6}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8CGT6}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8CGT6}. Note=Probable component of the meiotic
CC nuage, also named P granule, a germ-cell-specific organelle required to
CC repress transposon activity during meiosis. PIWIL2/MILI is required for
CC nuclear localization (By similarity). {ECO:0000250|UniProtKB:Q8CGT6}.
CC -!- TISSUE SPECIFICITY: Expressed in liver (PubMed:24930433). Expressed in
CC testis and pancreatic islets (PubMed:28711973).
CC {ECO:0000269|PubMed:24930433, ECO:0000269|PubMed:28711973}.
CC -!- PTM: Arginine methylation by PRMT5 is required for the interaction with
CC Tudor domain-containing protein (TDRD1, TDRKH/TDRD2 and TDRD9) and
CC subsequent localization to the meiotic nuage, also named P granule.
CC {ECO:0000250|UniProtKB:Q8CGT6}.
CC -!- SIMILARITY: Belongs to the argonaute family. Piwi subfamily.
CC {ECO:0000305}.
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DR EMBL; BC098798; AAH98798.1; -; mRNA.
DR AlphaFoldDB; Q4G033; -.
DR SMR; Q4G033; -.
DR STRING; 10116.ENSRNOP00000039460; -.
DR iPTMnet; Q4G033; -.
DR PhosphoSitePlus; Q4G033; -.
DR PaxDb; Q4G033; -.
DR UCSC; RGD:1311015; rat.
DR RGD; 1311015; Piwil4.
DR eggNOG; KOG1042; Eukaryota.
DR InParanoid; Q4G033; -.
DR PhylomeDB; Q4G033; -.
DR PRO; PR:Q4G033; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043186; C:P granule; ISS:UniProtKB.
DR GO; GO:0071547; C:piP-body; ISS:UniProtKB.
DR GO; GO:0034584; F:piRNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; ISS:UniProtKB.
DR GO; GO:0010669; P:epithelial structure maintenance; ISS:UniProtKB.
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:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR Gene3D; 3.30.420.10; -; 1.
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 Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 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 2: Evidence at transcript level;
KW Cytoplasm; Developmental protein; Differentiation; Meiosis; Methylation;
KW Nucleus; Reference proteome; RNA-binding; RNA-mediated gene silencing;
KW Spermatogenesis; Translation regulation.
FT CHAIN 1..848
FT /note="Piwi-like protein 4"
FT /id="PRO_0000367290"
FT DOMAIN 263..379
FT /note="PAZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT DOMAIN 541..834
FT /note="Piwi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00150"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 848 AA; 95971 MW; 957BBB10DFDE86C7 CRC64;
MSGRARVRAR GITTGHSARE VERAPRDLMV TSVSPGDNEA SSRTSVISQP HELGVSSGDG
RRTLVEKRGN GRQDFVDLGV CTREKLTHVK DSKTGSSGIP VQLATNLFHL DLPQDWQLYQ
YHVTYSPDLA SRRLRTALLY NHSILSDKAK AFDGTSLFLS EKLDHKVTEL TSETQRGETV
KITLTLTSEL FPNSPMCIQF FNVIFRKIFK KLSMYQIGRN YYKPSEPVEI PQYKLSLWPG
FAISVSRFES KLLVNADVNY KVLRNETVLE FMTDLCLRTD MSCFTETCHK QLVGLIVLTR
YNNKTYRIDD IDWSVKPTHA FQKRDGSETT YVDYYKQQYD ITLSDLNQPV LVSLLKRRRN
DNSEPQMVHL IPELCFLTGL TSQATSDFRL MKAVAEETRL SPMGRQQQLA RLADDIQRNQ
VTRFELETWG LHFGSQLSLT GRVVPSEKIL LQDHTCQPAF AADWSKDMRS CKVLSSEPLN
TWLIVCCSRA EHLIESFLSC LRRVGGSTGF SVGHPKIIKV DENPAAFLRA IQLHVNPDVQ
LVMCILPSNQ KNYYDSIKRY LSSDCPVPSQ CVLTRTLNKQ GMMLSVATKI AMQMTCKLGG
ELWAVEIPLK SLMVVGIDIC RDALSKDVAV VGFVASINSR ITRWFSRCVL QRTAADIADC
LKVCMTGALN KWYKHNHDLP ARIIAYRDGV GNGQLKAVLE YEVPQLLSSV TECGSDARSC
RLSVVVVRKR CLLRLFAESG HTLQNPPLGT VVDSEATRPE WYDFYLTSQT ANRGTVSPTY
YNVIYDDNAL KPDHMQRLTF KLCHLYYNWQ GVISVPAPCQ YAHKLTFLVA QSIHKEPSLE
LANKLFYL