PEG10_HUMAN
ID PEG10_HUMAN Reviewed; 708 AA.
AC Q86TG7; B4DSP0; Q96A68; Q9UPV1;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Retrotransposon-derived protein PEG10 {ECO:0000305};
DE AltName: Full=Embryonal carcinoma differentiation-regulated protein {ECO:0000250|UniProtKB:Q7TN75};
DE AltName: Full=Mammalian retrotransposon-derived protein 2 {ECO:0000250|UniProtKB:Q7TN75};
DE AltName: Full=Myelin expression factor 3-like protein 1 {ECO:0000303|Ref.2};
DE Short=MEF3-like protein 1 {ECO:0000303|Ref.2};
DE AltName: Full=Paternally expressed gene 10 protein {ECO:0000303|PubMed:11318613};
DE AltName: Full=Retrotransposon gag domain-containing protein 3;
DE AltName: Full=Retrotransposon-derived gag-like polyprotein {ECO:0000303|PubMed:15611116};
DE AltName: Full=Ty3/Gypsy-like protein {ECO:0000250|UniProtKB:Q7TN75};
GN Name=PEG10 {ECO:0000303|PubMed:11318613, ECO:0000312|HGNC:HGNC:14005};
GN Synonyms=EDR {ECO:0000250|UniProtKB:Q7TN75},
GN KIAA1051e {ECO:0000303|PubMed:10231032}, MAR2,
GN MART2 {ECO:0000250|UniProtKB:Q7TN75}, MEF3L1 {ECO:0000303|Ref.2}, RGAG3;
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], AND TISSUE SPECIFICITY.
RX PubMed=11318613; DOI=10.1006/geno.2001.6494;
RA Ono R., Kobayashi S., Wagatsuma H., Aisaka K., Kohda T., Kaneko-Ishino T.,
RA Ishino F.;
RT "A retrotransposon-derived gene, PEG10, is a novel imprinted gene located
RT on human chromosome 7q21.";
RL Genomics 73:232-237(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Satoh S., Furukawa Y.;
RT "Isolation of MEF3 like gene 1.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [4]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:BAG61702.1};
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
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 [9]
RP DEVELOPMENTAL STAGE.
RX PubMed=12620933; DOI=10.1095/biolreprod.102.013078;
RA Smallwood A., Papageorghiou A., Nicolaides K., Alley M.K.R., Jim A.,
RA Nargund G., Ojha K., Campbell S., Banerjee S.;
RT "Temporal regulation of the expression of syncytin (HERV-W), maternally
RT imprinted PEG10, and SGCE in human placenta.";
RL Biol. Reprod. 69:286-293(2003).
RN [10]
RP FUNCTION, INTERACTION WITH SIAH1 AND SIAH2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=12810624;
RA Okabe H., Satoh S., Furukawa Y., Kato T., Hasegawa S., Nakajima Y.,
RA Yamaoka Y., Nakamura Y.;
RT "Involvement of PEG10 in human hepatocellular carcinogenesis through
RT interaction with SIAH1.";
RL Cancer Res. 63:3043-3048(2003).
RN [11]
RP FUNCTION, INTERACTION WITH ACVRL1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15611116; DOI=10.1074/jbc.m409197200;
RA Lux A., Beil C., Majety M., Barron S., Gallione C.J., Kuhn H.-M.,
RA Berg J.N., Kioschis P., Marchuk D.A., Hafner M.;
RT "Human retroviral gag- and gag-pol-like proteins interact with the
RT transforming growth factor-beta receptor activin receptor-like kinase 1.";
RL J. Biol. Chem. 280:8482-8493(2005).
RN [12]
RP FUNCTION, INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16423995; DOI=10.1158/0008-5472.can-05-1553;
RA Li C.-M., Margolin A.A., Salas M., Memeo L., Mansukhani M., Hibshoosh H.,
RA Szabolcs M., Klinakis A., Tycko B.;
RT "PEG10 is a c-MYC target gene in cancer cells.";
RL Cancer Res. 66:665-672(2006).
RN [13]
RP INDUCTION.
RX PubMed=17050006; DOI=10.1016/j.bbamcr.2006.09.015;
RA Garcia-Alvarez G., Ventura V., Ros O., Aligue R., Gil J., Tauler A.;
RT "Glycogen synthase kinase-3beta binds to E2F1 and regulates its
RT transcriptional activity.";
RL Biochim. Biophys. Acta 1773:375-382(2007).
RN [14]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17621626; DOI=10.1002/ijc.22929;
RA Kainz B., Shehata M., Bilban M., Kienle D., Heintel D.,
RA Kroemer-Holzinger E., Le T., Kroeber A., Heller G., Schwarzinger I.,
RA Demirtas D., Chott A., Doehner H., Zoechbauer-Mueller S., Fonatsch C.,
RA Zielinski C., Stilgenbauer S., Gaiger A., Wagner O., Jaeger U.;
RT "Overexpression of the paternally expressed gene 10 (PEG10) from the
RT imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic
RT leukemia.";
RL Int. J. Cancer 121:1984-1993(2007).
RN [15]
RP RIBOSOMAL FRAMESHIFT, PROTEOLYTIC PROCESSING, MUTAGENESIS OF ASP-370, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=17942406; DOI=10.1074/jbc.m705676200;
RA Clark M.B., Jaenicke M., Gottesbuehren U., Kleffmann T., Legge M.,
RA Poole E.S., Tate W.P.;
RT "Mammalian gene PEG10 expresses two reading frames by high efficiency -1
RT frameshifting in embryonic-associated tissues.";
RL J. Biol. Chem. 282:37359-37369(2007).
RN [16]
RP RETRACTED PAPER.
RX PubMed=17369855; DOI=10.1038/sj.onc.1210362;
RA Jie X., Lang C., Jian Q., Chaoqun L., Dehua Y., Yi S., Yanping J.,
RA Luokun X., Qiuping Z., Hui W., Feili G., Boquan J., Youxin J., Jinquan T.;
RT "Androgen activates PEG10 to promote carcinogenesis in hepatic cancer
RT cells.";
RL Oncogene 26:5741-5751(2007).
RN [17]
RP INDUCTION.
RX PubMed=18625225; DOI=10.1016/j.febslet.2008.07.009;
RA Wang C., Xiao Y., Hu Z., Chen Y., Liu N., Hu G.;
RT "PEG10 directly regulated by E2Fs might have a role in the development of
RT hepatocellular carcinoma.";
RL FEBS Lett. 582:2793-2798(2008).
RN [18]
RP INDUCTION.
RX PubMed=20362226; DOI=10.1016/j.cancergencyto.2010.01.004;
RA Tsuji K., Yasui K., Gen Y., Endo M., Dohi O., Zen K., Mitsuyoshi H.,
RA Minami M., Itoh Y., Taniwaki M., Tanaka S., Arii S., Okanoue T.,
RA Yoshikawa T.;
RT "PEG10 is a probable target for the amplification at 7q21 detected in
RT hepatocellular carcinoma.";
RL Cancer Genet. Cytogenet. 198:118-125(2010).
RN [19]
RP RETRACTION NOTICE OF PUBMED:17369855.
RX PubMed=21677654; DOI=10.1038/onc.2011.66;
RA Jie X., Lang C., Jian Q., Chaoqun L., Dehua Y., Yi S., Yanping J.,
RA Luokun X., Qiuping Z., Hui W., Feili G., Boquan J., Youxin J., Jinquan T.;
RL Oncogene 30:2798-2798(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-321 (ISOFORM 2),
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP ALTERNATIVE INITIATION (ISOFORMS 3 AND 4), AND USE OF A NON-AUG INITIATOR
RP START CODON.
RX PubMed=20084274; DOI=10.1371/journal.pone.0008686;
RA Lux H., Flammann H., Hafner M., Lux A.;
RT "Genetic and molecular analyses of PEG10 reveal new aspects of genomic
RT organization, transcription and translation.";
RL PLoS ONE 5:e8686-e8686(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP FUNCTION, AND INDUCTION.
RX PubMed=26235627; DOI=10.1016/j.celrep.2015.07.012;
RA Akamatsu S., Wyatt A.W., Lin D., Lysakowski S., Zhang F., Kim S., Tse C.,
RA Wang K., Mo F., Haegert A., Brahmbhatt S., Bell R., Adomat H., Kawai Y.,
RA Xue H., Dong X., Fazli L., Tsai H., Lotan T.L., Kossai M., Mosquera J.M.,
RA Rubin M.A., Beltran H., Zoubeidi A., Wang Y., Gleave M.E., Collins C.C.;
RT "The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate
RT Cancer.";
RL Cell Rep. 12:922-936(2015).
RN [25]
RP FUNCTION, AND INDUCTION.
RX PubMed=28193232; DOI=10.1186/s13046-017-0500-x;
RA Peng Y.P., Zhu Y., Yin L.D., Zhang J.J., Wei J.S., Liu X., Liu X.C.,
RA Gao W.T., Jiang K.R., Miao Y.;
RT "PEG10 overexpression induced by E2F-1 promotes cell proliferation,
RT migration, and invasion in pancreatic cancer.";
RL J. Exp. Clin. Cancer Res. 36:30-30(2017).
RN [26]
RP INDUCTION.
RX PubMed=28992046; DOI=10.1093/jmcb/mjx034;
RA Wang D., Zhao J., Li S., Wei J., Nan L., Mallampalli R.K.,
RA Weathington N.M., Ma H., Zhao Y.;
RT "Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene
RT expression and activate lung epithelial cells.";
RL J. Mol. Cell Biol. 10:60-73(2018).
RN [27]
RP FUNCTION.
RX PubMed=30094509; DOI=10.1007/s00774-018-0946-8;
RA Yahiro Y., Maeda S., Shinohara N., Jokoji G., Sakuma D., Setoguchi T.,
RA Ishidou Y., Nagano S., Komiya S., Taniguchi N.;
RT "PEG10 counteracts signaling pathways of TGF-beta and BMP to regulate
RT growth, motility and invasion of SW1353 chondrosarcoma cells.";
RL J. Bone Miner. Metab. 37:441-454(2019).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND BIOTECHNOLOGY.
RX PubMed=34413232; DOI=10.1126/science.abg6155;
RA Segel M., Lash B., Song J., Ladha A., Liu C.C., Jin X., Mekhedov S.L.,
RA Macrae R.K., Koonin E.V., Zhang F.;
RT "Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be
RT pseudotyped for mRNA delivery.";
RL Science 373:882-889(2021).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 161-252, AND DOMAIN.
RX PubMed=34357660; DOI=10.1002/prot.26204;
RA Zurowska K., Alam A., Ganser-Pornillos B.K., Pornillos O.;
RT "Structural evidence that MOAP1 and PEG10 are derived from
RT retrovirus/retrotransposon Gag proteins.";
RL Proteins 90:309-313(2022).
CC -!- FUNCTION: Retrotransposon-derived protein that binds its own mRNA and
CC self-assembles into virion-like capsids (PubMed:34413232). Forms
CC virion-like extracellular vesicles that encapsulate their own mRNA and
CC are released from cells, enabling intercellular transfer of PEG10 mRNA
CC (PubMed:34413232). Binds its own mRNA in the 5'-UTR region, in the
CC region near the boundary between the nucleocapsid (NC) and protease
CC (PRO) coding sequences and in the beginning of the 3'-UTR region
CC (PubMed:34413232). Involved in placenta formation: required for
CC trophoblast stem cells differentiation (By similarity). Involved at the
CC immediate early stage of adipocyte differentiation (By similarity).
CC Overexpressed in many cancers and enhances tumor progression: promotes
CC cell proliferation by driving cell cycle progression from G0/G1
CC (PubMed:12810624, PubMed:16423995, PubMed:26235627, PubMed:28193232).
CC Enhances cancer progression by inhibiting the TGF-beta signaling,
CC possibly via interaction with the TGF-beta receptor ACVRL1
CC (PubMed:15611116, PubMed:26235627, PubMed:30094509). May bind to the
CC 5'-GCCTGTCTTT-3' DNA sequence of the MB1 domain in the myelin basic
CC protein (MBP) promoter; additional evidences are however required to
CC confirm this result (By similarity). {ECO:0000250|UniProtKB:Q7TN75,
CC ECO:0000269|PubMed:12810624, ECO:0000269|PubMed:15611116,
CC ECO:0000269|PubMed:16423995, ECO:0000269|PubMed:26235627,
CC ECO:0000269|PubMed:28193232, ECO:0000269|PubMed:30094509,
CC ECO:0000269|PubMed:34413232}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes into virion-like capsids (By
CC similarity). Interacts with ACVRL1 (PubMed:15611116). Interacts with
CC SIAH1 and SIAH2 (PubMed:12810624). {ECO:0000250|UniProtKB:Q7TN75,
CC ECO:0000269|PubMed:12810624, ECO:0000269|PubMed:15611116}.
CC -!- INTERACTION:
CC Q86TG7; Q13137: CALCOCO2; NbExp=4; IntAct=EBI-2858265, EBI-739580;
CC Q86TG7; O95751: LDOC1; NbExp=4; IntAct=EBI-2858265, EBI-740738;
CC Q86TG7; Q8N448: LNX2; NbExp=3; IntAct=EBI-2858265, EBI-2340947;
CC Q86TG7; Q17RB0: RTL8B; NbExp=3; IntAct=EBI-2858265, EBI-10238588;
CC Q86TG7; A6ZKI3: RTL8C; NbExp=3; IntAct=EBI-2858265, EBI-10174072;
CC Q86TG7; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-2858265, EBI-747107;
CC Q86TG7; Q9H0E2: TOLLIP; NbExp=2; IntAct=EBI-2858265, EBI-74615;
CC Q86TG7-2; Q9NQT4: EXOSC5; NbExp=3; IntAct=EBI-6259410, EBI-371876;
CC Q86TG7-2; O95751: LDOC1; NbExp=4; IntAct=EBI-6259410, EBI-740738;
CC Q86TG7-2; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-6259410, EBI-11984839;
CC Q86TG7-2; Q9BWD3: RTL8A; NbExp=8; IntAct=EBI-6259410, EBI-741643;
CC Q86TG7-2; Q17RB0: RTL8B; NbExp=11; IntAct=EBI-6259410, EBI-10238588;
CC Q86TG7-2; A6ZKI3: RTL8C; NbExp=10; IntAct=EBI-6259410, EBI-10174072;
CC -!- SUBCELLULAR LOCATION: Extracellular vesicle membrane
CC {ECO:0000269|PubMed:34413232}. Cytoplasm {ECO:0000269|PubMed:12810624,
CC ECO:0000269|PubMed:15611116, ECO:0000269|PubMed:16423995,
CC ECO:0000269|PubMed:17621626}. Nucleus {ECO:0000269|PubMed:12810624}.
CC Note=Forms virion-like extracellular vesicles that are released from
CC cells (PubMed:34413232). Detected predominantly in the cytoplasm of
CC breast and prostate carcinomas, in hepatocellular carcinoma (HCC) and
CC B-cell chronic lymphocytic leukemia (B-CLL) cells and in the Hep-G2
CC cell line (PubMed:12810624). {ECO:0000269|PubMed:12810624,
CC ECO:0000269|PubMed:34413232}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation, Ribosomal frameshifting; Named isoforms=5;
CC Name=1; Synonyms=RF1/RF2 {ECO:0000303|PubMed:17942406};
CC IsoId=Q86TG7-1; Sequence=Displayed;
CC Name=2; Synonyms=RF1 {ECO:0000303|PubMed:17942406};
CC IsoId=Q86TG7-2; Sequence=VSP_032007, VSP_032008;
CC Name=3;
CC IsoId=Q86TG7-3; Sequence=VSP_061361, VSP_032007, VSP_032008;
CC Name=4;
CC IsoId=Q86TG7-4; Sequence=VSP_061362;
CC Name=5;
CC IsoId=Q86TG7-5; Sequence=VSP_061362, VSP_032007, VSP_032008;
CC -!- TISSUE SPECIFICITY: Expressed in the cytotrophoblast layer but not in
CC the overlying syncytiotrophoblast of the placenta. Expressed in
CC prostate and breast carcinomas but not in normal breast and prostate
CC epithelial cells. Expressed in the Hep-G2 cell line (at protein level).
CC Expressed in brain, liver, spleen, kidney, thymus, lung, ovary, testis,
CC reactive lymph node, skeletal muscle, adipose tissue and placenta.
CC Expressed in pancreatic and hepatocellular carcinomas (HCC).
CC {ECO:0000269|PubMed:11318613, ECO:0000269|PubMed:12810624,
CC ECO:0000269|PubMed:15611116, ECO:0000269|PubMed:16423995,
CC ECO:0000269|PubMed:17621626}.
CC -!- DEVELOPMENTAL STAGE: Expressed in placenta during the first trimester
CC of gestation (at protein level). In placenta, down-regulated at early
CC hypoxic phase, and highly activated at 11-12 week of gestation.
CC {ECO:0000269|PubMed:12620933, ECO:0000269|PubMed:17942406}.
CC -!- INDUCTION: Expression is directly regulated by E2F1 and E2F4, which
CC bind to its promoter and direct its expression (PubMed:17050006,
CC PubMed:18625225, PubMed:28193232, PubMed:28992046). Up-regulated by MYC
CC (PubMed:16423995). Strongly overepressed in a number of tumors, such
CC has hepatocellular carcinoma (HCC), pancreatic or neuroendocrine
CC prostate cancers (PubMed:20362226, PubMed:26235627, PubMed:28193232).
CC {ECO:0000269|PubMed:16423995, ECO:0000269|PubMed:17050006,
CC ECO:0000269|PubMed:18625225, ECO:0000269|PubMed:20362226,
CC ECO:0000269|PubMed:26235627, ECO:0000269|PubMed:28193232,
CC ECO:0000269|PubMed:28992046}.
CC -!- DOMAIN: The protein is evolutionarily related to retrotransposon Gag
CC proteins: it contains the capsid (CA) and nucleocapsid (NC) subdomains
CC of gag. {ECO:0000269|PubMed:34357660, ECO:0000269|PubMed:34413232}.
CC -!- DOMAIN: [Isoform 1]: In addition to the capsid (CA) and nucleocapsid
CC (NC) subdomains of gag proteins, this isoform contains subdomains of
CC pol, namely a protease (PRO) domain and a predicted reverse
CC transcriptase (RT)-like domain. {ECO:0000269|PubMed:34413232}.
CC -!- PTM: [Isoform 1]: Undergoes proteolytic cleavage.
CC {ECO:0000269|PubMed:17942406}.
CC -!- BIOTECHNOLOGY: Can be reprogrammed to form virion-like capsids that
CC deliver engineered cargo mRNAs bearing RNA signals from PEG10 5'- and
CC 3'-UTR into target cells. {ECO:0000269|PubMed:34413232}.
CC -!- MISCELLANEOUS: The PEG10 locus is imprinted, giving rise to paternally
CC expressed proteins. {ECO:0000269|PubMed:11318613}.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by a -1 ribosomal frameshifting
CC due to a slippery site occurring between the codons for Gly-319 and
CC Lys-320 (PubMed:17942406). The ribosomal frameshifting efficiency yield
CC up to 66% of isoform 1 compared to isoform 2 (PubMed:17942406).
CC {ECO:0000269|PubMed:17942406}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by conventional translation.
CC {ECO:0000269|PubMed:17942406}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation
CC (PubMed:20084274). Translation initiates from a non-AUG codon (CUG
CC codon) (PubMed:20084274). {ECO:0000269|PubMed:20084274}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative initiation and
CC ribosomal frameshifting (PubMed:20084274). Produced by a -1 ribosomal
CC frameshifting due to a slippery site occurring between the codons for
CC Gly-395 and Lys-396 (PubMed:20084274). Translation initiates from a
CC non-AUG codon (CUG codon) (PubMed:20084274).
CC {ECO:0000269|PubMed:20084274}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative initiation
CC (Probable). Translation initiates from a non-AUG codon (CUG codon)
CC (Probable). {ECO:0000305}.
CC -!- CAUTION: Was reported to be activated by androgen receptor agonist
CC dihydrotestosterone (DHT) in hepatic cancer cells (HCC), resulting in
CC HCC growth and apoptotic resistance. However, this study was later
CC retracted. {ECO:0000305|PubMed:17369855, ECO:0000305|PubMed:21677654}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83003.2; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PEG10ID44104ch7q21.html";
CC ---------------------------------------------------------------------------
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DR EMBL; AB049834; BAB43951.1; -; mRNA.
DR EMBL; AB049150; BAB68387.1; -; mRNA.
DR EMBL; AB028974; BAA83003.2; ALT_SEQ; mRNA.
DR EMBL; AK299837; BAG61702.1; -; mRNA.
DR EMBL; AC069292; AAS07484.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76781.1; -; Genomic_DNA.
DR EMBL; BC050659; AAH50659.1; -; mRNA.
DR CCDS; CCDS55126.1; -. [Q86TG7-2]
DR CCDS; CCDS75636.1; -. [Q86TG7-5]
DR CCDS; CCDS75637.1; -. [Q86TG7-3]
DR RefSeq; NP_001035242.1; NM_001040152.1. [Q86TG7-2]
DR RefSeq; NP_001165908.1; NM_001172437.2.
DR RefSeq; NP_001165909.1; NM_001172438.2.
DR RefSeq; NP_001171890.1; NM_001184961.1.
DR RefSeq; NP_001171891.1; NM_001184962.1.
DR RefSeq; NP_055883.2; NM_015068.3. [Q86TG7-1]
DR PDB; 7LGA; X-ray; 1.90 A; A/B/D/E=161-238.
DR PDBsum; 7LGA; -.
DR AlphaFoldDB; Q86TG7; -.
DR SMR; Q86TG7; -.
DR BioGRID; 116717; 106.
DR ELM; Q86TG7; -.
DR IntAct; Q86TG7; 36.
DR MINT; Q86TG7; -.
DR STRING; 9606.ENSP00000418944; -.
DR GlyGen; Q86TG7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86TG7; -.
DR PhosphoSitePlus; Q86TG7; -.
DR SwissPalm; Q86TG7; -.
DR BioMuta; PEG10; -.
DR DMDM; 172046699; -.
DR EPD; Q86TG7; -.
DR jPOST; Q86TG7; -.
DR MassIVE; Q86TG7; -.
DR MaxQB; Q86TG7; -.
DR PaxDb; Q86TG7; -.
DR PeptideAtlas; Q86TG7; -.
DR PRIDE; Q86TG7; -.
DR ProteomicsDB; 69693; -. [Q86TG7-1]
DR ProteomicsDB; 69694; -. [Q86TG7-2]
DR Antibodypedia; 30119; 403 antibodies from 34 providers.
DR DNASU; 23089; -.
DR Ensembl; ENST00000482108.1; ENSP00000417587.1; ENSG00000242265.6. [Q86TG7-2]
DR Ensembl; ENST00000488574.5; ENSP00000418944.2; ENSG00000242265.6. [Q86TG7-5]
DR Ensembl; ENST00000615790.5; ENSP00000482653.2; ENSG00000242265.6. [Q86TG7-3]
DR GeneID; 23089; -.
DR KEGG; hsa:23089; -.
DR UCSC; uc011kie.3; human.
DR UCSC; uc064flv.1; human. [Q86TG7-1]
DR CTD; 23089; -.
DR DisGeNET; 23089; -.
DR GeneCards; PEG10; -.
DR HGNC; HGNC:14005; PEG10.
DR HPA; ENSG00000242265; Tissue enhanced (adrenal gland, brain, placenta).
DR MIM; 609810; gene.
DR neXtProt; NX_Q86TG7; -.
DR OpenTargets; ENSG00000242265; -.
DR PharmGKB; PA33170; -.
DR VEuPathDB; HostDB:ENSG00000242265; -.
DR eggNOG; ENOG502S3G3; Eukaryota.
DR GeneTree; ENSGT00950000183173; -.
DR HOGENOM; CLU_000384_20_1_1; -.
DR InParanoid; Q86TG7; -.
DR OrthoDB; 583605at2759; -.
DR PhylomeDB; Q86TG7; -.
DR TreeFam; TF335133; -.
DR PathwayCommons; Q86TG7; -.
DR SignaLink; Q86TG7; -.
DR BioGRID-ORCS; 23089; 10 hits in 1069 CRISPR screens.
DR ChiTaRS; PEG10; human.
DR GeneWiki; PEG10; -.
DR GenomeRNAi; 23089; -.
DR Pharos; Q86TG7; Tbio.
DR PRO; PR:Q86TG7; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q86TG7; protein.
DR Bgee; ENSG00000242265; Expressed in adrenal tissue and 192 other tissues.
DR ExpressionAtlas; Q86TG7; baseline and differential.
DR Genevisible; Q86TG7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:1903561; C:extracellular vesicle; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:HGNC-UCL.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0110077; P:vesicle-mediated intercellular transport; ISS:UniProtKB.
DR Gene3D; 2.40.70.10; -; 1.
DR Gene3D; 3.30.70.270; -; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR032549; DUF4939.
DR InterPro; IPR032567; LDOC1-rel.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR PANTHER; PTHR15503; PTHR15503; 1.
DR Pfam; PF16297; DUF4939; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Apoptosis; Coiled coil; Cytoplasm;
KW Differentiation; DNA-binding; Isopeptide bond; Membrane; Metal-binding;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Ribosomal frameshifting; RNA-binding; Transport; Transposable element;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..708
FT /note="Retrotransposon-derived protein PEG10"
FT /id="PRO_0000323026"
FT ZN_FING 293..310
FT /note="CCHC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 21..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 76..275
FT /note="Necessary for interaction with ACVRL1"
FT /evidence="ECO:0000269|PubMed:15611116"
FT REGION 310..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 683..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1..50
FT /evidence="ECO:0000255"
FT COMPBIAS 25..41
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 507
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q7TN75"
FT MOD_RES 598
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q7TN75"
FT MOD_RES 611
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q7TN75"
FT CROSSLNK 311
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7TN75"
FT CROSSLNK 314
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7TN75"
FT VAR_SEQ 1
FT /note="M -> MGPDCPPPPPPPPPNNNNNNNSKHTGHKSACVPNM (in isoform
FT 3)"
FT /id="VSP_061361"
FT VAR_SEQ 1
FT /note="M -> MRNKRVLKTKKRRSGRGGQDPGLHPHRSEATAGRSPPTPTVTLGPDC
FT PPPPPPPPPNNNNNNNSKHTGHKSACVPNM (in isoform 4 and isoform
FT 5)"
FT /id="VSP_061362"
FT VAR_SEQ 320..325
FT /note="KLPGPA -> NSPAPL (in isoform 2, isoform 3 and
FT isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_032007"
FT VAR_SEQ 326..708
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_032008"
FT MUTAGEN 370
FT /note="D->A: Inhibits proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:17942406"
FT HELIX 161..173
FT /evidence="ECO:0007829|PDB:7LGA"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:7LGA"
FT HELIX 199..209
FT /evidence="ECO:0007829|PDB:7LGA"
FT HELIX 212..218
FT /evidence="ECO:0007829|PDB:7LGA"
FT HELIX 227..238
FT /evidence="ECO:0007829|PDB:7LGA"
FT MOD_RES Q86TG7-2:316
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q86TG7-2:321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
SQ SEQUENCE 708 AA; 80173 MW; BFAA2FA24941D5D1 CRC64;
MTERRRDELS EEINNLREKV MKQSEENNNL QSQVQKLTEE NTTLREQVEP TPEDEDDDIE
LRGAAAAAAP PPPIEEECPE DLPEKFDGNP DMLAPFMAQC QIFMEKSTRD FSVDRVRVCF
VTSMMTGRAA RWASAKLERS HYLMHNYPAF MMEMKHVFED PQRREVAKRK IRRLRQGMGS
VIDYSNAFQM IAQDLDWNEP ALIDQYHEGL SDHIQEELSH LEVAKSLSAL IGQCIHIERR
LARAAAARKP RSPPRALVLP HIASHHQVDP TEPVGGARMR LTQEEKERRR KLNLCLYCGT
GGHYADNCPA KASKSSPAGK LPGPAVEGPS ATGPEIIRSP QDDASSPHLQ VMLQIHLPGR
HTLFVRAMID SGASGNFIDH EYVAQNGIPL RIKDWPILVE AIDGRPIASG PVVHETHDLI
VDLGDHREVL SFDVTQSPFF PVVLGVRWLS THDPNITWST RSIVFDSEYC RYHCRMYSPI
PPSLPPPAPQ PPLYYPVDGY RVYQPVRYYY VQNVYTPVDE HVYPDHRLVD PHIEMIPGAH
SIPSGHVYSL SEPEMAALRD FVARNVKDGL ITPTIAPNGA QVLQVKRGWK LQVSYDCRAP
NNFTIQNQYP RLSIPNLEDQ AHLATYTEFV PQIPGYQTYP TYAAYPTYPV GFAWYPVGRD
GQGRSLYVPV MITWNPHWYR QPPVPQYPPP QPPPPPPPPP PPPSYSTL
