EXD1_HUMAN
ID EXD1_HUMAN Reviewed; 514 AA.
AC Q8NHP7; A8K909; B7Z839; Q6ZW94;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=piRNA biogenesis protein EXD1 {ECO:0000305};
DE AltName: Full=Exonuclease 3'-5' domain-containing protein 1 {ECO:0000312|HGNC:HGNC:28507};
DE AltName: Full=Exonuclease 3'-5' domain-like-containing protein 1 {ECO:0000312|HGNC:HGNC:28507};
DE AltName: Full=Inactive exonuclease EXD1 {ECO:0000305};
GN Name=EXD1; Synonyms=EXDL1;
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 [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP ALA-489.
RC TISSUE=Hippocampus, and 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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).
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 (By similarity). 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:0000250|UniProtKB:Q8CDF7}.
CC -!- SUBUNIT: Homodimer (By similarity). Component of the PET complex, at
CC least composed of EXD1, PIWIL2, TDRD12 and piRNAs (By similarity).
CC {ECO:0000250|UniProtKB:H9IUR0, ECO:0000250|UniProtKB:Q8CDF7}.
CC -!- INTERACTION:
CC Q8NHP7; A0A0C4DGQ7: EML2; NbExp=3; IntAct=EBI-10192266, EBI-12112376;
CC Q8NHP7; O95834: EML2; NbExp=3; IntAct=EBI-10192266, EBI-1054588;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NHP7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHP7-2; Sequence=VSP_033987;
CC Name=3;
CC IsoId=Q8NHP7-3; Sequence=VSP_054898;
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:0000250|UniProtKB:Q8CDF7}.
CC -!- SIMILARITY: Belongs to the EXD1 family. {ECO:0000305}.
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DR EMBL; AK123414; BAC85610.1; -; mRNA.
DR EMBL; AK292524; BAF85213.1; -; mRNA.
DR EMBL; AK302864; BAH13825.1; -; mRNA.
DR EMBL; AC012652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022408; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030628; AAH30628.2; -; mRNA.
DR CCDS; CCDS10072.1; -. [Q8NHP7-1]
DR CCDS; CCDS66738.1; -. [Q8NHP7-3]
DR RefSeq; NP_001273370.1; NM_001286441.1. [Q8NHP7-3]
DR RefSeq; NP_689809.2; NM_152596.3. [Q8NHP7-1]
DR RefSeq; XP_011519600.1; XM_011521298.2. [Q8NHP7-3]
DR AlphaFoldDB; Q8NHP7; -.
DR SMR; Q8NHP7; -.
DR BioGRID; 127804; 6.
DR IntAct; Q8NHP7; 3.
DR STRING; 9606.ENSP00000415056; -.
DR iPTMnet; Q8NHP7; -.
DR PhosphoSitePlus; Q8NHP7; -.
DR BioMuta; EXD1; -.
DR DMDM; 317373564; -.
DR jPOST; Q8NHP7; -.
DR MassIVE; Q8NHP7; -.
DR PaxDb; Q8NHP7; -.
DR PeptideAtlas; Q8NHP7; -.
DR PRIDE; Q8NHP7; -.
DR ProteomicsDB; 6921; -.
DR ProteomicsDB; 73731; -. [Q8NHP7-1]
DR ProteomicsDB; 73732; -. [Q8NHP7-2]
DR Antibodypedia; 23259; 158 antibodies from 15 providers.
DR DNASU; 161829; -.
DR Ensembl; ENST00000314992.9; ENSP00000321029.5; ENSG00000178997.12. [Q8NHP7-1]
DR Ensembl; ENST00000458580.7; ENSP00000415056.2; ENSG00000178997.12. [Q8NHP7-3]
DR GeneID; 161829; -.
DR KEGG; hsa:161829; -.
DR MANE-Select; ENST00000458580.7; ENSP00000415056.2; NM_001286441.2; NP_001273370.1. [Q8NHP7-3]
DR UCSC; uc001znk.5; human. [Q8NHP7-1]
DR CTD; 161829; -.
DR DisGeNET; 161829; -.
DR GeneCards; EXD1; -.
DR HGNC; HGNC:28507; EXD1.
DR HPA; ENSG00000178997; Tissue enriched (testis).
DR neXtProt; NX_Q8NHP7; -.
DR OpenTargets; ENSG00000178997; -.
DR PharmGKB; PA164719420; -.
DR VEuPathDB; HostDB:ENSG00000178997; -.
DR eggNOG; KOG2405; Eukaryota.
DR GeneTree; ENSGT00390000003581; -.
DR HOGENOM; CLU_034376_1_0_1; -.
DR OMA; MEPTCME; -.
DR OrthoDB; 1535075at2759; -.
DR PhylomeDB; Q8NHP7; -.
DR TreeFam; TF315023; -.
DR PathwayCommons; Q8NHP7; -.
DR SignaLink; Q8NHP7; -.
DR BioGRID-ORCS; 161829; 11 hits in 1077 CRISPR screens.
DR ChiTaRS; EXD1; human.
DR GenomeRNAi; 161829; -.
DR Pharos; Q8NHP7; Tdark.
DR PRO; PR:Q8NHP7; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8NHP7; protein.
DR Bgee; ENSG00000178997; Expressed in right testis and 59 other tissues.
DR ExpressionAtlas; Q8NHP7; baseline and differential.
DR Genevisible; Q8NHP7; HS.
DR GO; GO:0043186; C:P granule; ISS:UniProtKB.
DR GO; GO:1990923; C:PET complex; ISS: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; ISS:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0034587; P:piRNA metabolic process; ISS: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 Alternative splicing; Cytoplasm; Meiosis; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing.
FT CHAIN 1..514
FT /note="piRNA biogenesis protein EXD1"
FT /id="PRO_0000337244"
FT DOMAIN 30..122
FT /note="3'-5' exonuclease"
FT /evidence="ECO:0000255"
FT REGION 384..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 384..398
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..229
FT /note="MEDSEFLAYVELLDEVEQGSVRAKASSVSLHAERTWMEKMKVEDLNVCEPAS
FT PAPEAPATSLLNDLKYSPSEEEEVTYTVINQFQQKFGAAILHIKKQNVLSVAAEGANVC
FT RHGKLCWLQVATNCRVYLFDIFLLGSRAFHNGLQMILEDKRILKVIHDCRWLSDCLSHQ
FT YGILLNNVFDTQVADVLQFSMETGGYLPNCITTLQESLIKHLQVAPKYLSFLEKRQKLI
FT -> MSHCAQPKTVIFFKVLLTVQRKLFYCL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033987"
FT VAR_SEQ 1..9
FT /note="MEDSEFLAY -> MDPSSDYHFLSQILWKRVKLTLVCGVFEGVLQHVDPNKI
FT VVLKKVKNVETGRSVPGVKLFFGHEIVN (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054898"
FT VARIANT 489
FT /note="T -> A (in dbSNP:rs522063)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043676"
FT CONFLICT 32
FT /note="A -> T (in Ref. 1; BAF85213)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 58335 MW; 77CDD6CF846886DA CRC64;
MEDSEFLAYV ELLDEVEQGS VRAKASSVSL HAERTWMEKM KVEDLNVCEP ASPAPEAPAT
SLLNDLKYSP SEEEEVTYTV INQFQQKFGA AILHIKKQNV LSVAAEGANV CRHGKLCWLQ
VATNCRVYLF DIFLLGSRAF HNGLQMILED KRILKVIHDC RWLSDCLSHQ YGILLNNVFD
TQVADVLQFS METGGYLPNC ITTLQESLIK HLQVAPKYLS FLEKRQKLIQ ENPEVWFIRP
VSPSLLKILA LEATYLLPLR LALLDEMMSD LTTLVDGYLN TYREGSADRL GGTEPTCMEL
PEELLQLKDF QKQRREKAAR EYRVNAQGLL IRTVLQPKKL VTETAGKEEK VKGFLFGKNF
RIDKAPSFTS QDFHGDVNLL KEESLNKQAT NPQHLPPTEE GETSEDSSNK LICTKSKGSE
DQRITQKEHF MTPKHEFQAS LSLKEETEQL LMVENKEDLK CTKQAVSMSS FPQETRVSPS
DTFYPIRKTV VSTLPPCPAL EKIDSWISPF LNLP
