LORF2_HUMAN
ID LORF2_HUMAN Reviewed; 1275 AA.
AC O00370;
DT 22-JAN-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=LINE-1 retrotransposable element ORF2 protein;
DE Short=ORF2p;
DE Includes:
DE RecName: Full=Reverse transcriptase;
DE EC=2.7.7.49;
DE Includes:
DE RecName: Full=Endonuclease;
DE EC=3.1.21.-;
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], AND FUNCTION.
RX PubMed=9140393; DOI=10.1038/ng0597-37;
RA Sassaman D.M., Dombroski B.A., Moran J.V., Kimberland M.L., Naas T.P.,
RA DeBerardinis R.J., Gabriel A., Swergold G.D., Kazazian H.H. Jr.;
RT "Many human L1 elements are capable of retrotransposition.";
RL Nat. Genet. 16:37-43(1997).
RN [2]
RP FUNCTION AS A REVERSE TRANSCRIPTASE.
RX PubMed=7516468; DOI=10.1128/mcb.14.7.4485-4492.1994;
RA Dombroski B.A., Feng Q., Mathias S.L., Sassaman D.M., Scott A.F.,
RA Kazazian H.H. Jr., Boeke J.D.;
RT "An in vivo assay for the reverse transcriptase of human retrotransposon L1
RT in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 14:4485-4492(1994).
RN [3]
RP FUNCTION AS AN ENDONUCLEASE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASN-14;
RP GLU-43; ASP-145; ASP-205; HIS-230 AND ASP-703.
RX PubMed=8945517; DOI=10.1016/s0092-8674(00)81997-2;
RA Feng Q., Moran J.V., Kazazian H.H. Jr., Boeke J.D.;
RT "Human L1 retrotransposon encodes a conserved endonuclease required for
RT retrotransposition.";
RL Cell 87:905-916(1996).
CC -!- FUNCTION: Has a reverse transcriptase activity required for target-
CC primed reverse transcription of the LINE-1 element mRNA, a crucial step
CC in LINE-1 retrotransposition. Has also an endonuclease activity that
CC allows the introduction of nicks in the chromosomal target DNA. Cleaves
CC DNA in AT-rich regions between a 5' stretch of purines and a 3' stretch
CC of pyrimidines, corresponding to sites of LINE-1 integration in the
CC genome. {ECO:0000269|PubMed:7516468, ECO:0000269|PubMed:8945517,
CC ECO:0000269|PubMed:9140393}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00405, ECO:0000269|PubMed:8945517};
CC -!- SUBUNIT: Interacts with MOV10. {ECO:0000250|UniProtKB:P11369}.
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 one estimate is that 80 to
CC 100 of those elements could be transcribed, translated and active in
CC any individual. An active LINE-1 encodes for 2 proteins translated from
CC a single RNA containing two non-overlapping ORFs, ORF1 and ORF2. ORF2p
CC is described in this entry as a representative of all ORF2p potentially
CC expressed by active elements. ORF1p is described in the related entry
CC AC Q9UN81.
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DR EMBL; U93569; AAC51271.1; -; Genomic_DNA.
DR PIR; B28096; B28096.
DR PIR; S23650; S23650.
DR PDB; 1VYB; X-ray; 1.80 A; A/B=1-238.
DR PDB; 2V0R; X-ray; 2.30 A; A/B=1-238.
DR PDB; 2V0S; X-ray; 1.80 A; A=1-238.
DR PDB; 7N8K; X-ray; 2.01 A; A/B=1-238.
DR PDB; 7N8S; X-ray; 2.79 A; A=1-238.
DR PDB; 7N94; X-ray; 2.85 A; A/B=1-238.
DR PDBsum; 1VYB; -.
DR PDBsum; 2V0R; -.
DR PDBsum; 2V0S; -.
DR PDBsum; 7N8K; -.
DR PDBsum; 7N8S; -.
DR PDBsum; 7N94; -.
DR AlphaFoldDB; O00370; -.
DR SMR; O00370; -.
DR IntAct; O00370; 3.
DR iPTMnet; O00370; -.
DR PhosphoSitePlus; O00370; -.
DR BioMuta; -; -.
DR MassIVE; O00370; -.
DR PaxDb; O00370; -.
DR PeptideAtlas; O00370; -.
DR PRIDE; O00370; -.
DR neXtProt; NX_O00370; -.
DR PathwayCommons; O00370; -.
DR Pharos; O00370; Tbio.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; O00370; protein.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003964; F:RNA-directed DNA polymerase activity; IDA:UniProtKB.
DR GO; GO:0009036; F:type II site-specific deoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:UniProtKB.
DR GO; GO:0032199; P:reverse transcription involved in RNA-mediated transposition; IDA:UniProtKB.
DR GO; GO:0032197; P:transposition, RNA-mediated; IMP:UniProtKB.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR000477; RT_dom.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF00078; RVT_1; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS50878; RT_POL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA recombination; Endonuclease; Hydrolase; Magnesium;
KW Metal-binding; Multifunctional enzyme; Nuclease; Nucleotidyltransferase;
KW Reference proteome; RNA-directed DNA polymerase; Transferase.
FT CHAIN 1..1275
FT /note="LINE-1 retrotransposable element ORF2 protein"
FT /id="PRO_0000425082"
FT DOMAIN 498..773
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT DOMAIN 1242..1260
FT /note="DUF1725"
FT REGION 1..239
FT /note="Endonuclease activity"
FT BINDING 600
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 702
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 703
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT MUTAGEN 14
FT /note="N->A: Loss of endonuclease activity and reduced
FT transposition efficiency."
FT /evidence="ECO:0000269|PubMed:8945517"
FT MUTAGEN 43
FT /note="E->A: Loss of endonuclease activity."
FT /evidence="ECO:0000269|PubMed:8945517"
FT MUTAGEN 145
FT /note="D->A: Loss of endonuclease activity and reduced
FT transposition efficiency."
FT /evidence="ECO:0000269|PubMed:8945517"
FT MUTAGEN 205
FT /note="D->G: Loss of endonuclease activity and reduced
FT transposition efficiency."
FT /evidence="ECO:0000269|PubMed:8945517"
FT MUTAGEN 230
FT /note="H->A: Loss of endonuclease activity and reduced
FT transposition efficiency."
FT /evidence="ECO:0000269|PubMed:8945517"
FT MUTAGEN 703
FT /note="D->Y: Reduced transposition efficiency."
FT /evidence="ECO:0000269|PubMed:8945517"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:1VYB"
FT HELIX 21..34
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1VYB"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 95..104
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 107..115
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1VYB"
FT HELIX 121..131
FT /evidence="ECO:0007829|PDB:1VYB"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:1VYB"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:7N94"
FT HELIX 163..174
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:1VYB"
FT HELIX 180..184
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:1VYB"
FT TURN 196..199
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:1VYB"
FT HELIX 211..216
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:1VYB"
FT STRAND 232..237
FT /evidence="ECO:0007829|PDB:1VYB"
SQ SEQUENCE 1275 AA; 149012 MW; 588703688E7129FF CRC64;
MTGSNSHITI LTLNVNGLNS PIKRHRLASW IKSQDPSVCC IQETHLTCRD THRLKIKGWR
KIYQANGKQK KAGVAILVSD KTDFKPTKIK RDKEGHYIMV KGSIQQEELT ILNIYAPNTG
APRFIKQVLS DLQRDLDSHT LIMGDFNTPL SILDRSTRQK VNKDTQELNS ALHQTDLIDI
YRTLHPKSTE YTFFSAPHHT YSKIDHIVGS KALLSKCKRT EIITNYLSDH SAIKLELRIK
NLTQSRSTTW KLNNLLLNDY WVHNEMKAEI KMFFETNENK DTTYQNLWDA FKAVCRGKFI
ALNAYKRKQE RSKIDTLTSQ LKELEKQEQT HSKASRRQEI TKIRAELKEI ETQKTLQKIN
ESRSWFFERI NKIDRPLARL IKKKREKNQI DTIKNDKGDI TTDPTEIQTT IREYYKHLYA
NKLENLEEMD TFLDTYTLPR LNQEEVESLN RPITGSEIVA IINSLPTKKS PGPDGFTAEF
YQRYKEELVP FLLKLFQSIE KEGILPNSFY EASIILIPKP GRDTTKKENF RPISLMNIDA
KILNKILANR IQQHIKKLIH HDQVGFIPGM QGWFNIRKSI NVIQHINRAK DKNHVIISID
AEKAFDKIQQ PFMLKTLNKL GIDGMYLKII RAIYDKPTAN IILNGQKLEA FPLKTGTRQG
CPLSPLLFNI VLEVLARAIR QEKEIKGIQL GKEEVKLSLF ADDMIVYLEN PIVSAQNLLK
LISNFSKVSG YKINVQKSQA FLYNNNRQTE SQIMGELPFT IASKRIKYLG IQLTRDVKDL
FKENYKPLLK EIKEDTNKWK NIPCSWVGRI NIVKMAILPK VIYRFNAIPI KLPMTFFTEL
EKTTLKFIWN QKRARIAKSI LSQKNKAGGI TLPDFKLYYK ATVTKTAWYW YQNRDIDQWN
RTEPSEIMPH IYNYLIFDKP EKNKQWGKDS LLNKWCWENW LAICRKLKLD PFLTPYTKIN
SRWIKDLNVK PKTIKTLEEN LGITIQDIGV GKDFMSKTPK AMATKDKIDK WDLIKLKSFC
TAKETTIRVN RQPTTWEKIF ATYSSDKGLI SRIYNELKQI YKKKTNNPIK KWAKDMNRHF
SKEDIYAAKK HMKKCSSSLA IREMQIKTTM RYHLTPVRMA IIKKSGNNRC WRGCGEIGTL
VHCWWDCKLV QPLWKSVWRF LRDLELEIPF DPAIPLLGIY PKDYKSCCYK DTCTRMFIAA
LFTIAKTWNQ PNCPTMIDWI KKMWHIYTME YYAAIKNDEF ISFVGTWMKL ETIILSKLSQ
EQKTKHRIFS LIGGN
