LORF1_HUMAN
ID LORF1_HUMAN Reviewed; 338 AA.
AC Q9UN81; Q15605;
DT 22-JAN-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=LINE-1 retrotransposable element ORF1 protein;
DE Short=L1ORF1p;
DE AltName: Full=LINE retrotransposable element 1;
DE AltName: Full=LINE1 retrotransposable element 1;
GN Name=L1RE1; Synonyms=LRE1;
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 [GENOMIC DNA].
RX PubMed=10401005; DOI=10.1093/hmg/8.8.1557;
RA Kimberland M.L., Divoky V., Prchal J., Schwahn U., Berger W.,
RA Kazazian H.H. Jr.;
RT "Full-length human L1 insertions retain the capacity for high frequency
RT retrotransposition in cultured cells.";
RL Hum. Mol. Genet. 8:1557-1560(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10655552; DOI=10.1093/hmg/9.3.421;
RA Santos F.R., Pandya A., Kayser M., Mitchell R.J., Liu A., Singh L.,
RA Destro-Bisol G., Novelletto A., Qamar R., Mehdi S.Q., Adhikari R.,
RA de Knijff P., Tyler-Smith C.;
RT "A polymorphic L1 retroposon insertion in the centromere of the human Y
RT chromosome.";
RL Hum. Mol. Genet. 9:421-430(2000).
RN [3]
RP FUNCTION IN LINE-1 RETROTRANSPOSITION.
RX PubMed=8945518; DOI=10.1016/s0092-8674(00)81998-4;
RA Moran J.V., Holmes S.E., Naas T.P., DeBerardinis R.J., Boeke J.D.,
RA Kazazian H.H. Jr.;
RT "High frequency retrotransposition in cultured mammalian cells.";
RL Cell 87:917-927(1996).
RN [4]
RP FUNCTION.
RX PubMed=11158327; DOI=10.1128/mcb.21.4.1429-1439.2001;
RA Wei W., Gilbert N., Ooi S.L., Lawler J.F., Ostertag E.M., Kazazian H.H.,
RA Boeke J.D., Moran J.V.;
RT "Human L1 retrotransposition: cis preference versus trans
RT complementation.";
RL Mol. Cell. Biol. 21:1429-1439(2001).
RN [5]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN A RIBONUCLEOPROTEIN COMPLEX.
RX PubMed=16183655; DOI=10.1093/hmg/ddi354;
RA Kulpa D.A., Moran J.V.;
RT "Ribonucleoprotein particle formation is necessary but not sufficient for
RT LINE-1 retrotransposition.";
RL Hum. Mol. Genet. 14:3237-3248(2005).
RN [6]
RP INTERACTION WITH DDX39A; HNRNPA1; SERBP1 AND YBX1, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF LEU-93; LEU-100; LEU-114; ARG-155; ASN-157; ARG-159;
RP GLU-165 AND 261-ARG-ARG-262.
RX PubMed=17562864; DOI=10.1128/mcb.00332-07;
RA Goodier J.L., Zhang L., Vetter M.R., Kazazian H.H. Jr.;
RT "LINE-1 ORF1 protein localizes in stress granules with other RNA-binding
RT proteins, including components of RNA interference RNA-induced silencing
RT complex.";
RL Mol. Cell. Biol. 27:6469-6483(2007).
RN [7]
RP FUNCTION AS A NUCLEIC ACID CHAPERONE, AND HOMOOLIGOMERIZATION.
RX PubMed=21937507; DOI=10.1093/nar/gkr728;
RA Callahan K.E., Hickman A.B., Jones C.E., Ghirlando R., Furano A.V.;
RT "Polymerization and nucleic acid-binding properties of human L1 ORF1
RT protein.";
RL Nucleic Acids Res. 40:813-827(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING, AND INTERACTION WITH MOV10.
RX PubMed=23093941; DOI=10.1371/journal.pgen.1002941;
RA Goodier J.L., Cheung L.E., Kazazian H.H. Jr.;
RT "MOV10 RNA helicase is a potent inhibitor of retrotransposition in cells.";
RL PLoS Genet. 8:E1002941-E1002941(2012).
RN [9]
RP FUNCTION, INTERACTION WITH TEX19.1, AND UBIQUITINATION.
RX PubMed=28806172; DOI=10.7554/elife.26152;
RA MacLennan M., Garcia-Canadas M., Reichmann J., Khazina E., Wagner G.,
RA Playfoot C.J., Salvador-Palomeque C., Mann A.R., Peressini P., Sanchez L.,
RA Dobie K., Read D., Hung C.C., Eskeland R., Meehan R.R., Weichenrieder O.,
RA Garcia-Perez J.L., Adams I.R.;
RT "Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse
RT embryonic stem cells.";
RL Elife 6:0-0(2017).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30122351; DOI=10.1016/j.cell.2018.07.022;
RA Warkocki Z., Krawczyk P.S., Adamska D., Bijata K., Garcia-Perez J.L.,
RA Dziembowski A.;
RT "Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s.";
RL Cell 0:0-0(2018).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 157-252, HOMOTRIMERIZATION,
RP RNA-BINDING, AND MUTAGENESIS OF ARG-159; ARG-206; ARG-210; ARG-211;
RP ILE-218; ARG-220; ARG-235 AND ARG-261.
RX PubMed=19139409; DOI=10.1073/pnas.0809964106;
RA Khazina E., Weichenrieder O.;
RT "Non-LTR retrotransposons encode noncanonical RRM domains in their first
RT open reading frame.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:731-736(2009).
RN [12]
RP STRUCTURE BY NMR OF 157-330, X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF
RP 104-330, RNA-BINDING, COILED COIL, AND MUTAGENESIS OF GLU-116; ASP-123;
RP GLY-132; LYS-133; ARG-135; LYS-137; LYS-140; ARG-141; ASN-142; ARG-206;
RP ARG-210; ARG-211; ILE-218; ARG-220; ARG-235; ARG-261 AND TYR-282.
RX PubMed=21822284; DOI=10.1038/nsmb.2097;
RA Khazina E., Truffault V., Buttner R., Schmidt S., Coles M.,
RA Weichenrieder O.;
RT "Trimeric structure and flexibility of the L1ORF1 protein in human L1
RT retrotransposition.";
RL Nat. Struct. Mol. Biol. 18:1006-1014(2011).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH APOBEC3D.
RX PubMed=27428332; DOI=10.1371/journal.pone.0157220;
RA Liang W., Xu J., Yuan W., Song X., Zhang J., Wei W., Yu X.F., Yang Y.;
RT "APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and
RT Influencing LINE Reverse Transcriptase Activity.";
RL PLoS ONE 11:e0157220-e0157220(2016).
CC -!- FUNCTION: Nucleic acid-binding protein which is essential for
CC retrotransposition of LINE-1 elements in the genome. Functions as a
CC nucleic acid chaperone binding its own transcript and therefore
CC preferentially mobilizing the transcript from which they are encoded.
CC {ECO:0000269|PubMed:11158327, ECO:0000269|PubMed:21937507,
CC ECO:0000269|PubMed:28806172, ECO:0000269|PubMed:30122351,
CC ECO:0000269|PubMed:8945518}.
CC -!- SUBUNIT: Homotrimer (via coiled coil domain). May also form larger
CC homooligomers. May interact with DDX39A, HNRNPA1, SERBP1 and YBX1.
CC Interacts with TEX19 and UBR2 (PubMed:28806172). Interacts with MOV10
CC (PubMed:23093941). Interacts with APOBEC3D; this interaction inhibits
CC LINE-1 retrotransposition (PubMed:27428332).
CC {ECO:0000269|PubMed:16183655, ECO:0000269|PubMed:23093941,
CC ECO:0000269|PubMed:27428332, ECO:0000269|PubMed:28806172}.
CC -!- INTERACTION:
CC Q9UN81; Q9UN81: L1RE1; NbExp=4; IntAct=EBI-722458, EBI-722458;
CC Q9UN81; Q92900: UPF1; NbExp=6; IntAct=EBI-722458, EBI-373471;
CC Q9UN81; Q8TE30; NbExp=15; IntAct=EBI-722458, EBI-8874509;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:17562864}.
CC Cytoplasm {ECO:0000269|PubMed:27428332}. Cytoplasm, Cytoplasmic
CC ribonucleoprotein granule {ECO:0000269|PubMed:16183655,
CC ECO:0000269|PubMed:30122351}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:17562864, ECO:0000269|PubMed:23093941}.
CC Note=Colocalizes with its encoding RNA in cytoplasmic ribonucleoprotein
CC particle (PubMed:16183655). Mainly cytoplasmic, rarely detected in the
CC nucleus, possibly within the nucleolus (PubMed:17562864).
CC {ECO:0000269|PubMed:16183655, ECO:0000269|PubMed:17562864}.
CC -!- DOMAIN: The coiled coil domain mediates homotrimerization.
CC -!- DOMAIN: The RRM and the CTD domain are both required for proper RNA-
CC binding activity.
CC -!- PTM: Polyubiquitinated, probably by UBR2, which induces its
CC degradation. {ECO:0000269|PubMed:28806172}.
CC -!- MISCELLANEOUS: Long interspersed element-1/LINE-1/L1 retrotransposons
CC are present in more than 500'000 full (6 kb) or truncated copies in the
CC human genome. Most of them are inactive but 80 to 100 of those elements
CC could be transcribed, translated and active in any individual. An
CC active LINE-1 encodes for 2 proteins translated from a single RNA
CC containing 2 non-overlapping ORFs, ORF1 and ORF2. ORF1p is described in
CC this entry as a representative of all ORF1p potentially expressed by
CC active elements. ORF2p is described in the related entry AC O00370.
CC -!- SIMILARITY: Belongs to the transposase 22 family. {ECO:0000305}.
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DR EMBL; AF148856; AAD39214.1; -; Genomic_DNA.
DR EMBL; M80343; AAB59367.1; -; Genomic_DNA.
DR PDB; 2LDY; NMR; -; A=157-330.
DR PDB; 2W7A; X-ray; 1.40 A; A/B=157-250.
DR PDB; 2YKO; X-ray; 2.10 A; A/B/C=106-330.
DR PDB; 2YKP; X-ray; 3.10 A; A/B/C=106-326.
DR PDB; 2YKQ; X-ray; 3.10 A; A/B/C=106-326.
DR PDB; 6FIA; X-ray; 2.65 A; A/B/C/D/E/F=53-152.
DR PDBsum; 2LDY; -.
DR PDBsum; 2W7A; -.
DR PDBsum; 2YKO; -.
DR PDBsum; 2YKP; -.
DR PDBsum; 2YKQ; -.
DR PDBsum; 6FIA; -.
DR AlphaFoldDB; Q9UN81; -.
DR BMRB; Q9UN81; -.
DR SMR; Q9UN81; -.
DR DIP; DIP-48676N; -.
DR IntAct; Q9UN81; 32.
DR MINT; Q9UN81; -.
DR iPTMnet; Q9UN81; -.
DR PhosphoSitePlus; Q9UN81; -.
DR BioMuta; HGNC:6686; -.
DR EPD; Q9UN81; -.
DR jPOST; Q9UN81; -.
DR MassIVE; Q9UN81; -.
DR MaxQB; Q9UN81; -.
DR PeptideAtlas; Q9UN81; -.
DR PRIDE; Q9UN81; -.
DR CPTC; Q9UN81; 2 antibodies.
DR MIM; 151626; gene.
DR neXtProt; NX_Q9UN81; -.
DR PathwayCommons; Q9UN81; -.
DR SignaLink; Q9UN81; -.
DR Pharos; Q9UN81; Tbio.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9UN81; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0032197; P:transposition, RNA-mediated; IDA:UniProtKB.
DR Gene3D; 3.30.250.20; -; 1.
DR InterPro; IPR042566; L1_C.
DR InterPro; IPR035300; L1_dsRBD.
DR InterPro; IPR043636; L1_RRM_dom.
DR InterPro; IPR035301; L1_trimer.
DR InterPro; IPR004244; Transposase_22.
DR PANTHER; PTHR11505; PTHR11505; 1.
DR Pfam; PF17490; Tnp_22_dsRBD; 1.
DR Pfam; PF17489; Tnp_22_trimer; 1.
DR Pfam; PF02994; Transposase_22; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Nucleotide-binding; Nucleus;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..338
FT /note="LINE-1 retrotransposable element ORF1 protein"
FT /id="PRO_0000425081"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 157..252
FT /note="RNA recognition motif (RRM) domain"
FT REGION 253..317
FT /note="C-terminal domain (CTD)"
FT COILED 49..153
FT /evidence="ECO:0000255"
FT COMPBIAS 7..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 93
FT /note="L->A: Small decrease in localization to stress
FT granules; when associated with A-100 and A-114."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 100
FT /note="L->A: Small decrease in localization to stress
FT granules; when associated with A-93 and A-114."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 114
FT /note="L->A: Small decrease in localization to stress
FT granules; when associated with A-93 and A-100."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 116
FT /note="E->A: Loss of LINE-1 retrotransposition without
FT affecting RNA-binding; when associated with A-123."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 123
FT /note="D->A: Loss of LINE-1 retrotransposition without
FT affecting RNA-binding; when associated with A-116."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 132
FT /note="G->I: Loss of LINE-1 retrotransposition without
FT affecting RNA-binding; when associated with I-135 and I-
FT 142."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 133
FT /note="K->S: Loss of LINE-1 retrotransposition with
FT decreased RNA-binding; when associated with A-137, A-140
FT and S-141."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 135
FT /note="R->I: Loss of LINE-1 retrotransposition without
FT effect on RNA-binding; when associated with I-132 and I-
FT 142."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 137
FT /note="K->A: Loss of LINE-1 retrotransposition with
FT decreased RNA-binding; when associated with S-133, A-140
FT and S-141."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 140
FT /note="K->A: Loss of LINE-1 retrotransposition with
FT decreased RNA-binding; when associated with S-133, A-137
FT and S-141."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 141
FT /note="R->S: Loss of LINE-1 retrotransposition with
FT decreased RNA-binding; when associated with S-133, A-137
FT and A-140."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 142
FT /note="N->I: Loss of LINE-1 retrotransposition without
FT effect on RNA-binding; when associated with I-132 and I-
FT 135."
FT /evidence="ECO:0000269|PubMed:21822284"
FT MUTAGEN 155
FT /note="R->A: No effect on subcellular localization; when
FT associated with A-157."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 157
FT /note="N->A: No effect on subcellular localization; when
FT associated with A-155. Complete loss of localization to
FT stress granules, slightly increased localization to the
FT nucleus; when associated with G-159."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 159
FT /note="R->A: Moderately alters RNA-binding activity."
FT /evidence="ECO:0000269|PubMed:19139409"
FT MUTAGEN 159
FT /note="R->G: Decreased localization to stress granules.
FT Complete loss of localization to stress granules, slightly
FT increased localization to the nucleus; when associated with
FT A-157."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 165
FT /note="E->G: No effect on cytoplasmic localization, may
FT increase nucleolar localization."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 206
FT /note="R->A: Loss of RNA-binding activity; when associated
FT with A-210 and A-211."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 210
FT /note="R->A: Loss of RNA-binding activity; when associated
FT with A-206 and A-211."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 211
FT /note="R->A: Loss of RNA-binding activity; when associated
FT with A-206 and A-210."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 218
FT /note="I->Y: Moderately alters RNA-binding activity."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 220
FT /note="R->A: Loss of LINE-1 retrotransposition without
FT affecting RNA-binding."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 235
FT /note="R->A: Loss of LINE-1 retrotransposition with
FT decreased RNA-binding."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 261..262
FT /note="RR->AA: Small decrease in localization to stress
FT granules."
FT /evidence="ECO:0000269|PubMed:17562864"
FT MUTAGEN 261
FT /note="R->A: Loss of LINE-1 retrotransposition with
FT decreased RNA-binding."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 261
FT /note="R->K: Loss of LINE-1 retrotransposition without
FT affecting RNA-binding."
FT /evidence="ECO:0000269|PubMed:19139409,
FT ECO:0000269|PubMed:21822284"
FT MUTAGEN 282
FT /note="Y->A: Loss of LINE-1 retrotransposition without
FT affecting RNA-binding."
FT /evidence="ECO:0000269|PubMed:21822284"
FT CONFLICT 251
FT /note="A -> V (in Ref. 2; AAB59367)"
FT /evidence="ECO:0000305"
FT HELIX 53..90
FT /evidence="ECO:0007829|PDB:6FIA"
FT HELIX 111..153
FT /evidence="ECO:0007829|PDB:2YKO"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:2YKO"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:2W7A"
FT HELIX 171..185
FT /evidence="ECO:0007829|PDB:2W7A"
FT HELIX 187..192
FT /evidence="ECO:0007829|PDB:2W7A"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:2W7A"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:2LDY"
FT STRAND 216..222
FT /evidence="ECO:0007829|PDB:2W7A"
FT HELIX 224..237
FT /evidence="ECO:0007829|PDB:2W7A"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:2W7A"
FT STRAND 245..251
FT /evidence="ECO:0007829|PDB:2W7A"
FT HELIX 255..263
FT /evidence="ECO:0007829|PDB:2YKO"
FT HELIX 265..273
FT /evidence="ECO:0007829|PDB:2YKO"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:2YKO"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:2YKO"
FT STRAND 285..299
FT /evidence="ECO:0007829|PDB:2YKO"
FT HELIX 300..307
FT /evidence="ECO:0007829|PDB:2YKO"
FT HELIX 311..317
FT /evidence="ECO:0007829|PDB:2YKO"
FT TURN 318..322
FT /evidence="ECO:0007829|PDB:2YKO"
SQ SEQUENCE 338 AA; 40056 MW; C9ED80C33ED37523 CRC64;
MGKKQNRKTG NSKTQSASPP PKERSSSPAT EQSWMENDFD ELREEGFRRS NYSELREDIQ
TKGKEVENFE KNLEECITRI TNTEKCLKEL MELKTKAREL REECRSLRSR CDQLEERVSA
MEDEMNEMKR EGKFREKRIK RNEQSLQEIW DYVKRPNLRL IGVPESDVEN GTKLENTLQD
IIQENFPNLA RQANVQIQEI QRTPQRYSSR RATPRHIIVR FTKVEMKEKM LRAAREKGRV
TLKGKPIRLT ADLSAETLQA RREWGPIFNI LKEKNFQPRI SYPAKLSFIS EGEIKYFIDK
QMLRDFVTTR PALKELLKEA LNMERNNRYQ PLQNHAKM
