EXD1_MOUSE
ID EXD1_MOUSE Reviewed; 570 AA.
AC Q8CDF7;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=piRNA biogenesis protein EXD1 {ECO:0000305};
DE AltName: Full=Exonuclease 3'-5' domain-containing protein 1 {ECO:0000312|MGI:MGI:3045306};
DE AltName: Full=Exonuclease 3'-5' domain-like-containing protein 1 {ECO:0000312|MGI:MGI:3045306};
DE AltName: Full=Inactive exonuclease EXD1 {ECO:0000305};
DE Short=mExd1 {ECO:0000303|PubMed:26669262};
GN Name=Exd1; Synonyms=Exdl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [4]
RP FUNCTION, IDENTIFICATION IN THE PET COMPLEX, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26669262; DOI=10.1016/j.molcel.2015.11.009;
RA Yang Z., Chen K.M., Pandey R.R., Homolka D., Reuter M., Janeiro B.K.,
RA Sachidanandam R., Fauvarque M.O., McCarthy A.A., Pillai R.S.;
RT "PIWI slicing and EXD1 drive biogenesis of nuclear piRNAs from cytosolic
RT targets of the mouse piRNA pathway.";
RL Mol. Cell 61:138-152(2016).
CC -!- FUNCTION: RNA-binding component of the PET complex, a multiprotein
CC complex required for the processing of piRNAs during spermatogenesis.
CC The piRNA metabolic process mediates the repression of transposable
CC elements during meiosis by forming complexes composed of piRNAs and
CC Piwi proteins and governs the methylation and subsequent repression of
CC transposable elements, preventing their mobilization, which is
CC essential for the germline integrity (PubMed:26669262). The PET complex
CC is required during the secondary piRNAs metabolic process for the
CC PIWIL2 slicing-triggered loading of PIWIL4 piRNAs. In the PET complex,
CC EXD1 probably acts as an RNA adapter. EXD1 is an inactive exonuclease
CC (By similarity). {ECO:0000250|UniProtKB:H9IUR0,
CC ECO:0000269|PubMed:26669262}.
CC -!- SUBUNIT: Homodimer (By similarity). Component of the PET complex, at
CC least composed of EXD1, PIWIL2, TDRD12 and piRNAs.
CC {ECO:0000250|UniProtKB:H9IUR0, ECO:0000269|PubMed:26669262}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:H9IUR0}.
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. {ECO:0000250|UniProtKB:H9IUR0}.
CC -!- DOMAIN: The 3'-5' exonuclease domain lacks the conserved Asp-Glu-Asp-
CC Asp (DEDD) residues that coordinates divalent ions essential for
CC exonuclease activity. {ECO:0000305|PubMed:19468303}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and display normal fertility but
CC show defective biogenesis of antisense piRNAs and activation of
CC transposons. Reduced sequences generated by Piwil2 slicing, impaired
CC biogenesis of Piwil4 piRNAs and derepressed LINE1 retrotransposons.
CC {ECO:0000269|PubMed:26669262}.
CC -!- SIMILARITY: Belongs to the EXD1 family. {ECO:0000305}.
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DR EMBL; AK030132; BAC26799.1; -; mRNA.
DR EMBL; AL844536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC092241; AAH92241.1; -; mRNA.
DR CCDS; CCDS16603.1; -.
DR RefSeq; NP_766445.1; NM_172857.2.
DR RefSeq; XP_006499554.1; XM_006499491.2.
DR RefSeq; XP_017173654.1; XM_017318165.1.
DR AlphaFoldDB; Q8CDF7; -.
DR SMR; Q8CDF7; -.
DR CORUM; Q8CDF7; -.
DR STRING; 10090.ENSMUSP00000054980; -.
DR iPTMnet; Q8CDF7; -.
DR PhosphoSitePlus; Q8CDF7; -.
DR PaxDb; Q8CDF7; -.
DR PRIDE; Q8CDF7; -.
DR ProteomicsDB; 267669; -.
DR Antibodypedia; 23259; 158 antibodies from 15 providers.
DR DNASU; 241624; -.
DR Ensembl; ENSMUST00000060009; ENSMUSP00000054980; ENSMUSG00000048647.
DR Ensembl; ENSMUST00000171024; ENSMUSP00000126713; ENSMUSG00000048647.
DR GeneID; 241624; -.
DR KEGG; mmu:241624; -.
DR UCSC; uc008ltu.1; mouse.
DR CTD; 161829; -.
DR MGI; MGI:3045306; Exd1.
DR VEuPathDB; HostDB:ENSMUSG00000048647; -.
DR eggNOG; KOG2405; Eukaryota.
DR GeneTree; ENSGT00390000003581; -.
DR HOGENOM; CLU_034376_1_0_1; -.
DR InParanoid; Q8CDF7; -.
DR OMA; MEPTCME; -.
DR OrthoDB; 1535075at2759; -.
DR PhylomeDB; Q8CDF7; -.
DR TreeFam; TF315023; -.
DR BioGRID-ORCS; 241624; 3 hits in 71 CRISPR screens.
DR PRO; PR:Q8CDF7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8CDF7; protein.
DR Bgee; ENSMUSG00000048647; Expressed in cleaving embryo and 110 other tissues.
DR ExpressionAtlas; Q8CDF7; baseline and differential.
DR Genevisible; Q8CDF7; MM.
DR GO; GO:0043186; C:P granule; ISS:UniProtKB.
DR GO; GO:1990923; C:PET complex; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0034587; P:piRNA metabolic process; IMP:UniProtKB.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR002562; 3'-5'_exonuclease_dom.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF01612; DNA_pol_A_exo1; 1.
DR SMART; SM00474; 35EXOc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Meiosis; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing.
FT CHAIN 1..570
FT /note="piRNA biogenesis protein EXD1"
FT /id="PRO_0000337245"
FT DOMAIN 135..307
FT /note="3'-5' exonuclease"
FT /evidence="ECO:0000255"
FT REGION 433..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 453..467
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 570 AA; 63962 MW; 701DF4EF86567B74 CRC64;
MDPSSDYHFL NQILWRRVKL TLVSGIFEGV LQHVDPNKIV VLKNVRNAES GRSVPGVKVF
FGHEILNVEL MDEAEGASGE KASAVSINTE RAGMEKVKNE DVNVCEPASP APEVPTSSLL
SDLKYCPSEE EEVTYTVIDQ FQQKFGAAML HIKKQSVLSV AAEGANVCRH GKLCWLQVAT
NSRVYLFDIF LLGSRAFNNG LQMILEDKRI LKVIHDCRWL SDCLSHQYGI MLNNVFDTQV
ADVLQFSMET GGFLPNCIST LQESLIRHLK VAPRYLFFLE ERQKRIQENP EIWLTRPLPP
SLLKILALET TYLLPLRLVL LDEVMSDLTT LVDGYLNTYR EGSADRLAGT EPACMELPAE
LLQLQDFQKQ RRERAVKEYR VNARGLLIRT PLHPKEPTAC TAGKEERVQG FLFYKTDGGD
QVPRFLCPKS HEDEKFLDKE SKQTTAKSQI VPPRKEGEAH KDSKNKPGCW ESAGPEDPRA
QKAHALPPTW ASQSQFSLKE EIEQLTVVGN KGALTSPKEG ALVSPSLLQE TWEAPTDTFH
LPEKAEVSTL PPCPALEKTD SWISPSLNLF
